Could perisinusoidal cells be regional stem cells of the liver? Stellate cells Stellate cells

For quotation: Kurysheva M.A. Liver fibrosis: past, present and future // Breast cancer. 2010. No. 28. S. 1713

Liver fibrosis is a local or diffuse increase in the amount connective tissue, extracellular matrix (collagen fibrous fabric in the perisinusoidal space) and the main path of progression of chronic diffuse liver diseases. There is no fibrosis in the early stages clinical manifestations, and only a histological examination of the biopsy specimen reveals excessive accumulation of connective tissue. Subsequently, fibrosis leads to the formation of regenerative nodes, vascular anastomoses - the formation of liver cirrhosis. Non-cirrhotic liver fibrosis is rare and is not considered in this work.

The processes of fibrosis in the liver have been studied for many years (Table 1), but only after the discovery of the role of stellate cells in fibrosis processes were new opportunities for antifibrotic therapy obtained.

Pathogenesis of liver fibrosis
Sinusoidal cells - endothelial, Kupffer cells, stellate cells (Ito cell, stellate cell, retinoid-storing cell, lipocyte), together with the area of hepatocytes facing the lumen of the sinusoids, form a functional unit. In addition to cells, in the sinusoid area there is an extracellular matrix (ECM), visible only in liver diseases. All cells that form sinusoids can participate in the formation of the ECM. Normally, there is a balance between fibrogenesis factors and antifibrotic factors. The main role in fibrosis is played by Ito cells, which produce profibrotic and antifibrotic factors. Antifibrotic factors include matrix metalloproteases (MMPs), which are involved in the destruction of ECM proteins (collagenases, gelatinases, stromolysins). MMP activity is suppressed by tissue inhibitors of matrix metalloproteases (TIMPs), which are also produced by Ito cells.
When the liver is damaged, biologically active substances are released that activate macrophages and sinusoid endothelium, releasing IL-1, TNFα, nitric oxide, endothelin, acting on Ito cells. Stellate cells upon activation, they produce platelet-activating factor PDGF and transforming growth factor TGFβ 1. Under the influence of TGFβ 1, Ito cells begin to activate themselves and migrate to areas of inflammation. There is a change in the phenotype of Ito cells - they transform into myofibroblasts, which continue to produce TGFβ 1, and begin to produce ECM. An imbalance between fibrotic and antifibrotic factors leads to a 3-10-fold increase in ECM components and a change in its composition (the predominance of collagen types I and III). Redistribution of the matrix into the space of Disse, its expansion, capillarization of sinusoids is accompanied by a disturbance in the exchange between hepatocytes and blood, shunting of the blood due to the development of false lobules and the development of liver cirrhosis. If the action of inflammatory mediators ceases, Ito cells again begin to produce profibrotic substances and a decrease in ECM components in the space of Disse occurs. Thus, fibrosis in the early stages of development is a reversible process.
The pathogenesis of liver fibrosis in chronic viral hepatitis is associated with the induction of inflammatory cell activity by infected hepatocytes, which leads to stimulation of Ito cells. In alcoholic liver disease, acetaldehyde and oxygen free radicals activate Ito cells. In addition, ethanol promotes the growth of gram-negative microflora in the intestine, increasing the level of lipopolysaccharides in the portal blood and activating Kupffer cells that produce TNFα, acting on Ito cells. The pathogenesis of liver fibrosis in nonalcoholic fatty liver disease is associated with hyperglycemia and insulin resistance, leading to increased levels of free fatty acids and hepatic steatosis, and free radicals and proinflammatory cytokines lead to apoptosis of hepatocytes and activation of inflammatory cells with the progression of liver fibrosis. In primary biliary cirrhosis, biliary cells secrete fibrogenic mediators that activate Ito cells, triggering fibrogenesis.

Reversibility of liver fibrosis
For a long time, liver fibrosis was considered an irreversible pathological condition. However, 50 years ago cases of reverse development of fibrosis after effective therapy hemochromatosis and Wilson-Konovalov disease, and subsequently, data on the reverse development of fibrosis in autoimmune hepatitis as a result of immunosuppressive therapy, secondary biliary cirrhosis after surgical decompression of the biliary tract, non-alcoholic steatohepatitis with weight loss, and alcoholic hepatitis with abstinence were repeatedly published.
Reversibility of fibrosis was observed with long-term abstinence from alcohol intake, when after 4-6 weeks a decrease in the content of type IV collagen, laminin and hyaluronic acid was detected in the walls of the sinusoids during biopsy and in the blood serum - regression of the process of “sinusoid capillarization” occurred. Changes reflecting the function of Ito cells were also noted - an increase in the level of MMP-2 and a decrease in the level of its inhibitor TIMMP-2. At certain time intervals, a decrease in the number of actin myofibrils was observed in the walls of the sinusoids, which indicates a drop in the activity of Ito stellate cells and their switching from the synthesis of the extracellular matrix to its degradation.
At the same time, only with the introduction of antiviral therapy into clinical practice, the concept of liver fibrosis, as a dynamic process with the possibility of both progression and regression, was recognized as a scientifically proven fact.
Progress has led to a clear understanding that liver fibrosis is reversible and to realistic expectations that effective antifibrotic therapy will significantly change the management of patients with liver disease and provide a favorable prognosis even in those with established cirrhosis.
Diagnosis of liver fibrosis
The gold standard for diagnosing liver fibrosis is a biopsy with histological examination. Histological assessment is carried out according to Desmet scales (1984) as modified by Serov; JSHAK or METAVIR scale. Depending on the location and prevalence, the following forms of liver fibrosis are distinguished: venular and perivenular (in the center of the lobules and the walls of the central veins - characteristic of chronic alcoholic hepatitis); pericellular (around hepatocytes in chronic viral and alcoholic hepatitis); septal (concentric growth of fibrous tissue around the bile canaliculi - with viral hepatitis); portal and periportal (for viral, alcoholic, autoimmune hepatitis); periductal fibrosis (around the bile canaliculi in sclerosing cholangitis); mixed (different forms of fibrosis are presented).
Due to the invasiveness, the rather large error of histological examination associated with “mistakes in the needle” during puncture biopsy of the liver, and differences in the interpretation of results, for the early diagnosis of pathological processes, great attention is currently paid to non-invasive methods for diagnosing fibrosis. These include bioprognostic laboratory tests; liver elastometry and MR elastography; Ultrasound, CT, MRI of the liver, Doppler ultrasound of the vessels of the liver and spleen with calculation of indices of fibrosis and portal hypertension.
Markers of fibrosis are divided into direct (biomarkers), reflecting ECM metabolism, and indirect, indicating liver failure. Direct markers include carboxy-terminal peptide of type I procollagen, amino-terminal peptide of type III procollagen, TIMP-1, 2, type IV collagen, hyaluronic acid, laminin, MMP-2. The determination of these substances is used in clinical studies.
For clinical practice Various calculated prognostic indices have been proposed to assess the severity of liver fibrosis using indirect markers: APRI, ELF, FIB-4, FibroFast, FibroIndex, FibroMeter, FPI, Forns, GUCI, Hepascore, HALT-C, MDA, PGA, PGAA.
To assess the severity of liver fibrosis, the Fibro-test and Acti-test systems are used, considering them as an alternative to biopsy. Fibro test includes 5 biochemical parameters: alpha 2-macroglobulin (activates Ito cells), haptoglobin (reflects stimulation of liver cells by interleukins), apolipoprotein A1, gamma-glutamyl transpeptidase, total bilirubin. Acti-test (viral necroinflammatory activity is assessed) in addition to the listed components includes alanine aminotransferase - ALT. FibroMax is a combination of five non-invasive tests: FibroTest and ActiTest, Steato-Test (diagnoses liver steatosis), NeshTest (diagnoses non-alcoholic steatohepatitis), AshTest (diagnoses severe alcoholic steatohepatitis). FibroMax detects alpha 2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, total bilirubin, ALT, AST, glucose, triglycerides, cholesterol. Based on the data obtained, taking into account the age and gender of the patient, the stage of fibrosis and the level of hepatitis activity are calculated. The use of tests is limited by signs of cholestasis, which negatively affect the diagnostic value of the tests, and the high cost of the study.
The operation of the device, based on ultrasound elastography of the liver by passing waves (vibrations) through the liver and capturing them with a sensor, allows one to assess the degree of fibrosis in the liver in the early stages. The device is of little information for obesity and ascites.
Magnetic resonance elastography is a direct method for determining liver density, allowing the determination of F0 in comparison with healthy volunteers, which has not yet been demonstrated using other methods for assessing fibrosis.
In the future, it is possible to determine the presence and rate of fibrosis progression depending on the etiological factor. Solving these problems makes it possible to diagnose the early stages of fibrosis and, therefore, effectively treat it.

Treatment
Antifibrotic therapy is inextricably linked with the etiological and pathogenetic treatment of chronic hepatitis (Table 2). In most cases, drugs to eliminate etiological factors hepatitis are also antifibrotic agents. An antifibrotic effect was detected in antiviral drugs, pentoxifylline, phosphatidylcholine, glucocorticosteroids, nitric oxide donors, vitamin E, endothelin receptor antagonists, angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, silymarin. A search is underway for drugs that inhibit fibrogenesis for use in situations where the effect on the causative factor is difficult: antioxidants (betaine, probucol, N-acetylcysteine), hepatoprotectors (silymarin, UDCA, S-adenosylmethionine, essential phospholipids), reducing the activity of tumor necrosis factor (pentoxifylline , adiponectin, infliximab).
A search is underway for drugs with targeted antifibrotic effects:
- elimination of the damaging agent (interleukin 10, TNF inhibitors - anti-inflammatory effect; antioxidants - suppression of fibrotic processes in response to oxidative stress);
- suppression of profibrotic activity of stellate cells (interferons, hepatocyte growth factor, PPARγ agonists);
- maintaining active antifibrotic activity of stellate cells (TGFβ 1 antagonists - reduce matrix synthesis and increase its breakdown; PDGF antagonists, nitric oxide, ACE inhibitors - suppress the proliferation of Ito cells);
- influence on the secretion of collagens by stellate cells of the liver (ACE inhibitors, polyhydroxylase inhibitors, interferon γ - reduce fibrosis; endothelin receptor antagonists - reduce fibrosis and portal hypertension);
- effect on apoptosis of Ito cells (hylotoxin, NGF - neuronal growth factor - stimulate apoptosis);
- increased breakdown of the collagen matrix (metalloproteinases, tissue inhibitor MMP antagonists; TGFβ 1 antagonists - reduce TIMP activity and increase MMP activity; relaxin - reduce TIMP activity and increase MMP activity).
The use of the drug silymarin (Legalon) for antifibrotic purposes seems promising. Silymarin is the official name of a group of four flavonolignan isomers (silibinin, isosilibinin, silicristin and silydianin), isolated from extracts of the fruits of milk thistle (Cardui mariae fructus) and included in Legalon 70 and 140 (silymarin dose).
When conducting clinical trials It was found that, along with anti-inflammatory, antioxidant, antitoxic, hypolipidemic and anticarcinogenic effects, silymarin has a pronounced antifibrotic effect. This is due to effects on transforming growth factor β and gene expression in Ito cells, as well as increased free radical clearance and direct inhibition of collagen synthesis.
The relationship between the pharmacodynamics of silymarin/silibinin and the clinical effect of Legalon® is given in Table 3. The indicated mechanisms of action determine the therapeutic value of Legalon® in diffuse liver diseases. Numerous studies have shown the high effectiveness of Legalon® with long-term use in suppressing the inflammatory-necrotic reaction in the liver, inhibiting the development of fibrosis and reducing the risk of malignant transformation of hepatocytes in liver cirrhosis.
In a model of alcoholic liver fibrosis in monkeys, a morphological study of the liver and a study of serum markers of fibrosis revealed that animals treated with silymarin had significantly less fibrosis progression and less often developed liver cirrhosis.
The effect of Legalon on liver fibrosis was studied in 792 patients with chronic liver diseases, including cirrhosis. The P-III-NP indicator was chosen as a marker of fibrogenesis. The observation period averaged 107 days. When initially elevated level P-III-NP after 3 months of treatment with Legalon, the level of P-III-NP decreased to normal.
The results of 5 international placebo-controlled studies (600 patients participated) showed that the 4-year survival rate of patients with alcoholic cirrhosis while taking Legalon was statistically significantly higher compared to the group of patients receiving placebo. When analyzing subgroups, it was revealed that treatment with Legalon was effective in alcoholic cirrhosis, regardless of its severity and stage of cirrhosis, and in the subgroup with Chaid-Pugh stage A cirrhosis, regardless of its etiology. In the subgroup of patients with alcoholic cirrhosis due to viral hepatitis, no deaths were recorded during the observation period, while in the placebo group there were 4 deaths from decompensation of cirrhosis.
Fibrosis is currently called the cornerstone of chronic liver pathology. It is this that causes the formation of liver cirrhosis, therefore early diagnosis and treatment of fibrosis are extremely relevant at present and are a task for the future scientific research.

Literature
1. Sherlock Sh, Dooley J. Diseases of the liver and biliary tract: A practical guide. M.: GEOTAR-MED, 2002. 864 p.
2. Bataller R., Brenner D. A. Liver fibrosis. J. Clin. Invest. 2005; 115(2):209-218.
3. Iredale J. P. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J. Clin. Invest. 2007; 117(3):539-548.
4. Parsons C. J., Takashima M., Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol. 2007; 22(1):79-84.
5. Storozhakov G.I., Ivkova A.N. Pathogenetic aspects of fibrogenesis in chronic liver diseases. Wedge. Perspectives on Gastroenterology, Hepatology 2009; 2:3-10.
6. Pavlov Ch.S., Zolotarevsky V.B., Tomkevich M.S. Possibilities of reversibility of liver cirrhosis. Ross. Journal of Gastroenterology, Hepatology and Coloproctology 2006; 1:20-29.
7. Severov M.V. Reversibility of liver fibrosis and cirrhosis in HCV infection. Hepatology Forum 2008; 1:2-6.
8. Pavlov Ch.S., Glushenkov D.V., Ivashkin V.T. Modern features elastometry, fibro- and acti-test in the diagnosis of liver fibrosis. Ross. Journal of Gastroenterology, Hepatology and Coloproctology 2008; 4:43-52.
9. Rockey D.C. Antifibrotic therapy in chronic liver disease Clin. Gastroenterol. Hepatol. 2005; 3:95-107.
10. Dehmlow C, Erhard J. Hepatology 1996; 23:749-754.
11. Lieber et al. Gastroenterol. 2003; 37:336-339.
12. Schuppan, Z. Allg. Med. 1998; 74:577-584.

Intercellular communication might be realized by paracrine secretion and direct cell-to-cell contacts. It is known that hepatic perisinusoidal cells (HPC) establish regional stem cells niche and determine their differentiation. At the same time, HPC remains poorly characterized on molecular and cellular level.

The aim of the project was to study interactions between rat hepatic perisinusoidal cells and various stem cells such as mononuclear cell fraction of human umbilical cord blood (UCB-MC) and rat bone-marrow derived multipotential mesenchymal stromal cells (BM-MMSC).

Materials and methods. Rat BM-MSC and HPC, human UCB-MC cells were derived using standard techniques. To study HPC paracrine regulation we co-cultured UCB-MC or BM-MMSC cells with HPC using Boyden chambers and conditioned HPC cells media. Differentially labeled cells were co-cultured and their interactions were observed by phase-contrast fluorescent microscopy and immunocytochemistry.

Results. During the first week of cultivation there was autofluorescence of vitamin A because of fat-storing ability of PHC. BM-MMSC demonstrated high viability in all co-cultural models. After 2 day incubation in conditioned media co-culture of BM-MMSC with HPC we observed changes in morphology of MMSC - they decreased in size and their sprouts became shorter. The expression of α-Smooth Muscle Actin and desmin was similar to myofibroblast - an intermediate form of Ito cells culture in vitro. These changes could be due to paracrine stimulation by HPC. The most profound effect of HPC on UCB-MC cells was observed in contact co-culture, thereby it is important for UCB-MC cells to create direct cell-to-cell contacts for maintaining their viability. We did not observe any cell fusion between HPC /UCB and HPC /BM-MMSC cells in co-cultures. In our further experiments we plan to study growth factors produced by HPC for hepatic differentiation of stem cells.

Introduction.

Of particular interest among the diversity of liver cells are liver perisinusoidal cells (Ito cells). Thanks to the secretion of growth factors and components of the intercellular matrix, they create a microenvironment of hepatocytes, and a number of scientific studies have shown the ability of liver stellate cells to form a microenvironment for progenitor cells (including hematopoietic ones) and influence their differentiation into hepatocytes. Cell-to-cell interactions of these cell populations may occur through paracrine secretion of growth factors or direct cell-to-cell contacts, but the molecular and cellular basis of these processes remain poorly understood.

Purpose of the study.

Study of interaction mechanisms Ito cells with hematopoietic (HSC) and mesenchymal (MMSC) stem cells under in vitro conditions.

Materials and methods.

Rat liver Ito cells were isolated by two different enzymatic methods. Simultaneously from bone marrow stromal MMSCs were obtained from rats. The mononuclear fraction of hematopoietic stem cells was isolated from cord blood person. The paracrine influences of Ito cells were studied by culturing MMSCs and HSCs in the medium in which Ito cells grew, and by co-cultivating cells separated by a semipermeable membrane. The influence of intercellular contacts was studied during co-culture of cells. For better visualization, each population was labeled with an individual fluorescent tag. Cell morphology was assessed by phase contrast and fluorescence microscopy. Phenotypic characteristics of cultured cells were studied using immunocytochemical analysis.

Results.

Within a week after isolating perisinusoidal cells, we noted their ability to autofluorescent due to their fat-accumulating ability. Next, the cells entered an intermediate phase of their growth and acquired a stellate shape. At the initial stages of co-cultivation of Ito cells with rat bone marrow MMSCs, the viability of MMSCs was maintained in all cultivation options. On the second day, when MMSCs were cultivated in the culture medium of Ito cells, a change in the morphology of MMSCs occurred - they decreased in size, and their processes shortened. The expression of alpha-smooth muscle actin and desmin in MMSCs increased, indicating their phenotypic similarity to myofibroblasts, an intermediate growth stage of activated Ito cells in vitro. Our data indicate the influence of paracrine factors secreted by Ito cells on the properties of MMSCs in culture.

Based on co-cultivation of hematopoietic stem cells with Ito cells, it was shown that hematopoietic stem cells retain viability only during contact co-cultivation with Ito cells. According to the fluorescent analysis of mixed cultures, the phenomenon of fusion of cells of different populations was not detected.

Conclusions. To maintain the viability of hematopoietic stem cells, the presence of direct intercellular contacts with Ito cells is a decisive factor. Paracrine regulation was observed only when MMSCs were cultured in nutrient medium, in which Ito cells grew. It is planned to study the influence of specific factors produced by Ito cells on the differentiation of HSCs and MMSCs in cell culture in the following studies.

Shafigullina A.K., Trondin A.A., Shaikhutdinova A.R., Kaligin M.S., Gazizov I.M., Rizvanov A.A., Gumerova A.A., Kiyasov A.P.
GOU VPO "Kazan State Medical University Federal Agency for Health and Social Development"

Structure endothelial cells, Kupffer and Ito cells, we will look at the example of two figures.

The picture to the right of the text shows sinusoidal capillaries (SC) of the liver- intralobular capillaries of sinusoidal type, increasing from the entrance venules to the central vein. Hepatic sinusoidal capillaries form an anastomotic network between the hepatic plates. The lining of sinusoidal capillaries is formed by endothelial cells and Kupffer cells.

The picture to the left of the text shows the hepatic plate (LP) and two sinusoidal capillary (SC) of the liver sliced vertically and horizontally to show perisinusoidal Ito cells (Ito). The cut bile canaliculi (BC) are also marked in the figure.

Endothelial cells (EC)- highly flattened scaly cells with an elongated small nucleus, poorly developed organelles and a large number of micropinocytotic vesicles. The cytomembrane is dotted with irregular openings (O) and fenestrae, often grouped into cribriform plates (RP). These holes allow blood plasma to pass through, but not blood cells, allowing it access to hepatocytes (D). Endothelial cells do not have a basement membrane and do not exhibit phagocytosis. They are connected to each other using small connecting complexes (not shown). Together with Kupffer cells, endothelial cells form the internal border of the space of Disse (PD); its outer border is formed by hepatocytes.

Kupffer cells (KC)- large, non-persistent stellate cells within the hepatic sinusoidal capillaries, partly at their bifurcations.

Kupffer cell processes pass without any connecting devices between endothelial cells and often cross the lumen of the sinusoids. Kupffer cells contain an oval nucleus, many mitochondria, a well-developed Golgi complex, short cisterns of granular endoplasmic reticulum, many lysosomes (L), residual bodies and rare annular plates. Kupffer cells also include large phagolysosomes (PLs), which often contain obsolete red blood cells and foreign substances. Inclusions of hemosiderin or iron can also be detected, especially with supravital staining.

The surface of Kupffer cells displays variable, flattened cytoplasmic folds called lamellipodia (LP) - lamellar stalks - as well as processes called filopodia (F) and microvilli (MV) covered with glycocalyx. The plasmalemma forms vermiform bodies (VB) with a centrally located dense line. These structures may represent a condensed glycocalyx.

Kupffer cells- these are macrophages, very likely forming an independent genus of cells. They usually originate from other Kupffer cells due to the latter's mitotic division, but can also originate from the bone marrow. Some authors believe that they are activated endothelial cells.

Occasionally, an occasional autonomic nerve fiber (ANF) passes through the space of Disse. In some cases, the fibers have contact with hepatocytes. The edges of hepatocytes are delimited by interhepatocyte recesses (MU) dotted with microvilli.

These are stellate cells localized within the spaces of Disse (SD). Their nuclei are rich in condensed chromatin and are usually deformed by large lipid droplets (LDs). The latter are present not only in the perikaryon, but also in the processes of the cell and are visible from the outside as spherical protrusions. Organelles are poorly developed. Perisinusoidal cells show weak endocytotic activity but do not possess phagosomes. The cells have several long processes (O) that contact neighboring hepatocytes, but do not form connecting complexes.

The processes cover sinusoidal capillaries of the liver and in some cases pass through the hepatic plates, coming into contact with adjacent hepatic sinusoids. The processes are not constant, branched and thin; they can also be flattened. By accumulating groups of lipid droplets, they lengthen and take on the appearance of a bunch of grapes.

It is believed that perisinusoidal Ito cells- these are poorly differentiated mesenchymal cells that can be considered as hematopoietic stem cells, since they can transform into fat cells, active blood stem cells or fibroblasts.

IN normal conditions Ito cells are involved in the accumulation of fat and vitamin A as well as in the production of intralobular reticular and collagen fibers (KB).

In this case, these cells respond by multiplying to the influence of cytokines, growth factors and chemokines (pro-inflammatory cytokines) produced by the damaged liver. Chronic activation of stellate cells in response to replication-induced oxidative stress HBV virus and HCV, may contribute to fibrogenesis and increased proliferation of hepatocytes chronically infected with HBV and HCV.

Thus, stellate cells take part in the regulation of growth, differentiation and turnover of hepatocytes, which, together with the activation of MAP kinases, can lead to the development of liver cancer [Block, 2003].

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Studying the influence of liver Ito cells on stem cells

Shafigullina A.K., Trondin A.A., Shaikhutdinova A.R., Kaligin M.S., Gazizov I.M., Rizvanov A.A., Gumerova A.A., Kiyasov A.P.

State Educational Institution of Higher Professional Education "Kazan State Medical University of the Federal Agency for Health and Social Development"

Experimental assessment of osteoinductivity of recombinant bone morphogenetic protein

Cellular technologies in the treatment of degenerative diseases of bones and joints

Ito cage

calm And activated. Activated Ito cells

calm state

perisinusoidal(subendothelial) and interhepatocellular. The first leave the cell body and extend along the surface of the sinusoidal capillary, covering it with thin finger-like branches. The perisinusoidal projections are covered with short villi and have characteristic long microshoots that extend even further along the surface of the capillary endothelial tube. Interhepatocellular projections, having overcome the plate of hepatocytes and reaching the adjacent sinusoid, are divided into several perisinusoidal projections. Thus, on average, an Ito cell covers slightly more than two adjacent sinusoids.

activated state

Liver cells

The human liver is made up of cells, like any organic tissue. Nature has designed it in such a way that this organ performs the most important functions: it cleanses the body, produces bile, accumulates and deposits glycogen, synthesizes plasma proteins, manages metabolic processes, and participates in normalizing the amount of cholesterol and other components necessary for the functioning of the body.

To fulfill their purpose, liver cells must be healthy, have a stable structure, and each person must protect them from destruction.

About the structure and types of liver lobules

The cellular composition of the organ is characterized by diversity. Liver cells form lobules, and segments are made up of lobules. The structure of the organ is such that hepatocytes (the main liver cells) are located around the central vein, branch from it, connect with each other, forming sinusoids, that is, gaps filled with blood. Blood moves through them as if through capillaries. The liver is supplied with blood from the portal vein and artery located in the organ. The liver lobules produce bile and discharge it into the flow channels.

Other types of liver cells and their purpose

Endothelial - cells lining the sinusoids and containing fenestrae. The latter are intended to form a stepped barrier between the sinusoid and the Disse space.
The space of Disse itself is filled with stellate cells; they ensure the outflow of tissue fluid into the lymph vessels of the portal zones.
Kupffer cells are associated with the endothelium, they are attached to it, their function is to protect the liver when a generalized infection enters the body, or during injury.
Pit cells are killers of hepatocytes affected by the virus; in addition, they have cytotoxicity to tumor cells.

The human liver consists of 60% hepatocytes and 40% other types of cellular compounds. Hepatocytes have a polyhedron shape; there are at least 250 billion of them. The normal functioning of hepatocytes is determined by the spectrum of components that are secreted by the sinusoidal cells that fill the sinusoidal compartment. That is, the Kupffer listed above, stellate and pit cells (intrahepatic lymphocytes).

The endothelial is a filter between the blood in the sinusoidal space and the plasma in the Disse space. This biological filter sorts out large compounds that are excessively rich in retinol and cholesterol and does not allow them to pass through, which is beneficial for the body. In addition, their function is to protect the liver (namely hepatocytes) from mechanical damage by blood cells.

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The process of interaction of organ elements

There is an interaction between all particles of the organ, which has a rather complex pattern. A healthy liver is characterized by stable cellular connections, with pathological processes The extracellular matrix is visible under the microscope.

Organ tissue undergoes changes under the influence of toxins, for example, alcohol, viral agents. They are as follows:

deposition in the organ of products formed due to metabolic disorders;
cell degeneration;
hepatocyte necrosis;
fibrosis of liver tissue;
inflammatory process of the liver;
cholestasis.

About the treatment of organ pathology

It is useful for each patient to know what the changes that the organ undergoes mean. Not all of them are catastrophic. For example, dystrophy can be mild or severe. Both of these processes are reversible. Currently, there are drugs that restore cells and entire segments of the liver.

Cholestasis can be cured even with folk remedies - decoctions and infusions. They help normalize the synthesis of bilirubin and eliminate disturbances in the outflow of bile into duodenum.

With cirrhosis in initial stage treatment begins with a diet, then hepatoprotector therapy is prescribed. Most effective way Treatment of cirrhosis and fibrosis are stem cells, which are injected into the umbilical vein or intravenously; they restore hepatocytes damaged by various agents.

The main causes of liver cell death are alcohol abuse and drug exposure, including drugs and medications. Any toxin that enters the body is a liver destroyer. Therefore, you should give up bad habits so that you have a healthy liver.

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Education: Rostov State Medical University (RostSMU), Department of Gastroenterology and Endoscopy.

ENDOTHELIAL CELLS, KUPFER CELLS AND ITO

We will look at the structure of endothelial cells, Kupffer and Ito cells, using the example of two drawings.

The figure to the right of the text shows the sinusoidal capillaries (SC) of the liver - intralobular capillaries of the sinusoidal type, increasing from the entrance venules to the central vein. Hepatic sinusoidal capillaries form an anastomotic network between the hepatic plates. The lining of sinusoidal capillaries is formed by endothelial cells and Kupffer cells.

In the figure to the left of the text, the hepatic plate (LP) and the two sinusoidal capillaries (SCs) of the liver are cut vertically and horizontally to show the perisinusoidal Ito cells (Ito cells). The cut bile canaliculi (BC) are also marked in the figure.

ENDOTHELIAL CELLS

Endothelial cells (EC) are highly flattened squamous cells with an elongated small nucleus, poorly developed organelles and a large number of micropinocytotic vesicles. The cytomembrane is dotted with irregular openings (O) and fenestrae, often grouped into cribriform plates (RP). These holes allow blood plasma to pass through, but not blood cells, allowing it access to hepatocytes (D). Endothelial cells do not have a basement membrane and do not exhibit phagocytosis. They are connected to each other using small connecting complexes (not shown). Together with Kupffer cells, endothelial cells form the internal border of the space of Disse (PD); its outer border is formed by hepatocytes.

KUPFER CELLS

Kupffer cells (KCs) are large, non-persistent stellate cells within the hepatic sinusoidal capillaries, partly at their bifurcations.

Kupffer cells are macrophages, very likely forming an independent genus of cells. They usually originate from other Kupffer cells due to mitotic division of the latter, but can also originate from the bone marrow. Some authors believe that they are activated endothelial cells.

ITO CELLS

The processes envelop the sinusoidal capillaries of the liver and in some cases pass through the hepatic plates, coming into contact with adjacent hepatic sinusoids. The processes are not constant, branched and thin; they can also be flattened. By accumulating groups of lipid droplets, they lengthen and take on the appearance of a bunch of grapes.

It is believed that perisinusoidal Ito cells are poorly differentiated mesenchymal cells that can be considered hematopoietic stem cells, since they can transform into fat cells, active blood stem cells or fibroblasts under pathological conditions.

Under normal conditions, Ito cells are involved in the accumulation of fat and vitamin A as well as in the production of intralobular reticular and collagen fibers (KB).

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Ito liver cells

Universal online popular science encyclopedia

LIVER

LIVER, the largest gland in the body of vertebrates. In humans, it makes up about 2.5% of body weight, on average 1.5 kg in adult men and 1.2 kg in women. The liver is located in the upper right part abdominal cavity; it is attached by ligaments to the diaphragm, abdominal wall, stomach and intestines and is covered with a thin fibrous membrane - Glisson's capsule. The liver is a soft but dense organ of red-brown color and usually consists of four lobes: large right lobe, smaller left and much smaller caudate and quadrate lobes, forming the posterior lower surface of the liver.

Functions.

The liver is an essential organ for life with many different functions. One of the main ones is the formation and secretion of bile, clear liquid orange or yellow. Bile contains acids, salts, phospholipids (fats containing a phosphate group), cholesterol and pigments. Bile salts and free bile acids emulsify fats (i.e. break them into small droplets), making them easier to digest; convert fatty acids into water-soluble forms (which is necessary for the absorption of both the fatty acids themselves and fat-soluble vitamins A, D, E and K); have an antibacterial effect.

All nutrients absorbed into the blood from the digestive tract - products of the digestion of carbohydrates, proteins and fats, minerals and vitamins - pass through the liver and are processed there. At the same time, some amino acids (protein fragments) and some fats are converted into carbohydrates, so the liver is the largest “depot” of glycogen in the body. It synthesizes blood plasma proteins - globulins and albumin, and also undergoes amino acid conversion reactions (deamination and transamination). Deamination - the removal of nitrogen-containing amino groups from amino acids - allows the latter to be used, for example, for the synthesis of carbohydrates and fats. Transamination is the transfer of an amino group from an amino acid to a keto acid to form another amino acid ( cm. METABOLISM). Also synthesized in the liver ketone bodies(products of fatty acid metabolism) and cholesterol.

The liver is involved in regulating glucose (sugar) levels in the blood. If this level increases, liver cells convert glucose into glycogen (a substance similar to starch) and store it. If the blood glucose level drops below normal, glycogen is broken down and glucose enters the bloodstream. In addition, the liver is capable of synthesizing glucose from other substances, such as amino acids; this process is called gluconeogenesis.

Another function of the liver is detoxification. Medicines and other potentially toxic compounds can be converted into a water-soluble form in liver cells, which allows them to be excreted in bile; they can also be destroyed or conjugate (combine) with other substances to form harmless products that are easily excreted from the body. Some substances are temporarily deposited in Kupffer cells (special cells that absorb foreign particles) or in other liver cells. Kupffer cells are particularly effective at removing and destroying bacteria and other foreign particles. Thanks to them, the liver plays an important role in the body's immune defense. Possessing a dense network of blood vessels, the liver also serves as a blood reservoir (it constantly contains about 0.5 liters of blood) and is involved in the regulation of blood volume and blood flow in the body.

In general, the liver performs more than 500 different functions, and its activity cannot yet be reproduced artificially. Removal of this organ inevitably leads to death within 1–5 days. However, the liver has a huge internal reserve, it has an amazing ability to recover from damage, so humans and other mammals can survive even after 70% of the liver tissue is removed.

Structure.

The complex structure of the liver is perfectly adapted to perform its unique functions. The lobes consist of small structural units - lobules. In the human liver there are about one hundred thousand of them, each 1.5–2 mm long and 1–1.2 mm wide. The lobule consists of liver cells - hepatocytes, located around the central vein. Hepatocytes are united into layers one cell thick - the so-called. liver plates. They diverge radially from the central vein, branch and connect with each other, forming a complex system of walls; the narrow gaps between them, filled with blood, are known as sinusoids. Sinusoids are equivalent to capillaries; passing one into another, they form a continuous labyrinth. The hepatic lobules are supplied with blood from the branches of the portal vein and hepatic artery, and the bile formed in the lobules enters the tubular system, from them into the bile ducts and is excreted from the liver.

The hepatic portal vein and hepatic artery provide the liver with an unusual, dual blood supply. Enriched nutrients blood from the capillaries of the stomach, intestines and several other organs is collected in the portal vein, which, instead of carrying blood to the heart, like most other veins, carries it to the liver. In the liver lobules, the portal vein breaks up into a network of capillaries (sinusoids). The term “portal vein” indicates an unusual direction of blood transport from the capillaries of one organ to the capillaries of another (the kidneys and pituitary gland have a similar circulatory system).

The second source of blood supply to the liver, the hepatic artery, carries oxygenated blood from the heart to the outer surfaces of the lobules. The portal vein provides 75–80%, and the hepatic artery 20–25% of the total blood supply to the liver. In general, about 1500 ml of blood passes through the liver per minute, i.e. quarter cardiac output. Blood from both sources ultimately enters the sinusoids, where it mixes and flows to the central vein. From the central vein, the outflow of blood to the heart begins through the lobar veins into the hepatic vein (not to be confused with the portal vein of the liver).

Bile is secreted by liver cells into the smallest tubules between the cells - bile capillaries. Through the internal system of tubules and ducts it is collected into bile duct. Some of the bile goes directly into the common bile duct and is poured into the small intestine, but most of the bile is returned to the cystic duct for storage in the small intestine. gallbladder- a small pouch with muscular walls attached to the liver. When food enters the intestines, the gallbladder contracts and releases the contents into the common bile duct, which opens into the duodenum. The human liver produces about 600 ml of bile per day.

Portal triad and acini.

The branches of the portal vein, hepatic artery and bile duct are located nearby, at the outer border of the lobule and form the portal triad. At the periphery of each lobule there are several such portal triads.

The functional unit of the liver is the acinus. This is the part of tissue that surrounds the portal triad and includes lymphatic vessels, nerve fibers and adjacent sectors of two or more lobules. One acini contains about 20 liver cells located between the portal triad and central vein each slice. In a two-dimensional image, a simple acinus looks like a group of vessels surrounded by adjacent sections of lobules, and in a three-dimensional image it looks like a berry (acinus - lat. berry) hanging on a stalk of blood and bile vessels. Acinus, the microvascular framework of which consists of the above circulatory and lymphatic vessels, sinusoids and nerves, is the microcirculatory unit of the liver.

Liver cells

(hepatocytes) have the shape of polyhedra, but they have three main functional surfaces: sinusoidal, facing the sinusoidal channel; tubular - involved in the formation of the wall of the bile capillary (it does not have its own wall); and intercellular - directly adjacent to neighboring liver cells.

Ito cage

Ito cells (synonyms: hepatic stellate cell, fat-storing cell, lipocyte, English. Hepatic Stellate Cell, HSC, Cell of Ito, Ito cell) - pericytes contained in the perisinusoidal space of the hepatic lobule, capable of functioning in two different states - calm And activated. Activated Ito cells play main role in fibrogenesis - the formation of scar tissue during liver damage.

In an intact liver, stellate cells are found in calm state. In this state, the cells have several projections covering the sinusoidal capillary. Another distinctive feature cells is the presence in their cytoplasm of reserves of vitamin A (retinoid) in the form of fat drops. Quiet Ito cells make up 5-8% of all liver cells.

Ito cell outgrowths are divided into two types: perisinusoidal(subendothelial) and interhepatocellular. The first leave the cell body and extend along the surface of the sinusoidal capillary, covering it with thin finger-like branches. The perisinusoidal projections are covered with short villi and have characteristic long microshoots that extend even further along the surface of the capillary endothelial tube. Interhepatocellular projections, having overcome the plate of hepatocytes and reaching the adjacent sinusoid, are divided into several perisinusoidal projections. Thus, on average, an Ito cell covers slightly more than two adjacent sinusoids.

When the liver is damaged, Ito cells become activated state. The activated phenotype is characterized by proliferation, chemotaxis, contractility, loss of retinoid stores, and the formation of myofibroblast-like cells. Activated hepatic stellate cells also show increased content new genes such as α-SMA, ICAM-1, chemokines and cytokines. Activation indicates the beginning early stage fibrogenesis and precedes increased production of ECM proteins. The final stage of liver healing is characterized by increased apoptosis of activated Ito cells, as a result of which their number is sharply reduced.

Gold chloride staining is used to visualize Ito cells under microscopy. It has also been established that a reliable marker for differentiating these cells from other myofibroblasts is their expression of the Reelin protein.

Story

In 1876, Karl von Kupfer described cells he called "Sternzellen" (stellate cells). When stained with gold oxide, inclusions were visible in the cytoplasm of the cells. Mistakenly considering them to be fragments of red blood cells captured by phagocytosis, Kupfer in 1898 revised his views on the “stellate cell” as a separate type of cell and classified them as phagocytes. However, in subsequent years, descriptions of cells similar to Kupffer's “stellate cells” appeared regularly. They were assigned various names: interstitial cells, parasinusoid cells, lipocytes, pericytes. The role of these cells remained a mystery for 75 years, until Professor Toshio Ito discovered certain cells containing fat inclusions in the perisinusoidal space of the human liver. Ito called them "shibo-sesshu saibo" - fat-absorbing cells. Realizing that the inclusions were fat produced by cells from glycogen, he changed the name to “shibo-chozo saibo” - fat-storing cells. In 1971, Kenjiro Wake proved the identity of Kupffer's Sternzellen and Ito's fat-storing cells. Vake also found that these cells play an important role in storing vitamin A (prior to this it was believed that vitamin A was stored in Kupffer cells). Shortly thereafter, Kent and Popper demonstrated the close association of Ito cells with liver fibrosis. These discoveries began the process of studying Ito cells in detail.

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Links

Young-O Queon, Zachary D. Goodman, Jules L. Dienstag, Eugene R. Schiff, Nathaniel A. Brown, Elmar Burkhardt, Robert Schoonhoven, David A. Brenner, Michael W. Fried (2001). Journal of Haepothology 35; 749-755. - translation of an article in the journal “Infections and antimicrobial therapy", Volume 04/N 3/2002, on the Consilium-Medicum website.
Popper H: Distribution of vitamin A in tissue as revealed by fluorescence microscopy. Physiol Rev 1944, 24:.

Notes

Geerts A. (2001) History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 21(3):311-35. PMID
Wake, K. (1988) Liver perivascular cells revealed by gold- and silver-impregnation method and electron microscopy. In “Biopathology of the Liver. An Ultrastructural Approach" (Motta, P. M., ed) pp. 23-36, Kluwer Academic Publishers, Dordrecht, Netherlands
Stanciu A, Cotutiu C, Amalinei C. (2002) New data about ITO cells. Rev Med Chir Soc Med Nat Iasi. 107(2):235-9. PMID
John P. Iredale (2001) Hepatic Stellate Cell Behavior During Resolution of Liver Injury. Seminars in Liver Disease, 21(3):PMID- (English) on Medscape.
Kobold D, Grundmann A, Piscaglia F, Eisenbach C, Neubauer K, Steffgen J, Ramadori G, Knittel T. (2002) Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts. J Hepatol. 36(5):607-13. PMID
Adrian Reuben (2002) Hepatology. Volume 35, Issue 2, Pages 503-504 (English)
Suematsu M, Aiso S. (2001) Professor Toshio Ito: a clairvoyant in pericyte biology. Keio J Med. 50(2):66-71. PMID (English)
Querner F: Der mikroskopische Nachweis von Vitamin A im animalen Gewebe. Zur Kenntnis der paraplasmatischen Leberzellen-einschlüsse. Dritte Mitteilung. Klin Wschr 1935, 14:.

Excerpt characterizing Ito's Cell

Half an hour later, Kutuzov left for Tatarinova, and Bennigsen and his retinue, including Pierre, went along the line.

Bennigsen from Gorki descended along the high road to the bridge, which the officer from the mound pointed out to Pierre as the center of the position and on the bank of which lay rows of mown grass that smelled of hay. They drove across the bridge to the village of Borodino, from there they turned left and past a huge number of troops and cannons they drove out to a high mound on which the militia was digging. It was a redoubt that did not yet have a name, but later received the name Raevsky redoubt, or barrow battery.

Pierre did not pay much attention to this redoubt. He did not know that this place would be more memorable for him than all the places in the Borodino field. Then they drove through the ravine to Semenovsky, in which the soldiers were taking away the last logs of the huts and barns. Then, downhill and uphill, they drove forward through broken rye, knocked out like hail, along a road newly laid by artillery along the ridges of arable land to the flushes [a type of fortification. (Note by L.N. Tolstoy.) ], also still being dug at that time.

Bennigsen stopped at the flushes and began to look ahead at the Shevardinsky redoubt (which was ours only yesterday), on which several horsemen could be seen. The officers said that Napoleon or Murat was there. And everyone looked greedily at this bunch of horsemen. Pierre also looked there, trying to guess which of these barely visible people was Napoleon. Finally, the riders rode off the mound and disappeared.

Bennigsen turned to the general who approached him and began to explain the entire position of our troops. Pierre listened to Bennigsen's words, straining all his mental strength to understand the essence of the upcoming battle, but he felt with disappointment that his mental abilities were insufficient for this. He didn't understand anything. Bennigsen stopped talking, and noticing the figure of Pierre, who was listening, he suddenly said, turning to him:

– I think you’re not interested?

“Oh, on the contrary, it’s very interesting,” Pierre repeated, not entirely truthfully.

From the flush they drove even further to the left along a road winding through a dense, low birch forest. In the middle of it

forest, a brown hare with white legs jumped out onto the road in front of them and, frightened by the clatter of a large number of horses, he was so confused that he jumped along the road in front of them for a long time, arousing everyone’s attention and laughter, and only when several voices shouted at him, he rushed to the side and disappeared into the thicket. After driving about two miles through the forest, they came to a clearing where the troops of Tuchkov’s corps, which was supposed to protect the left flank, were stationed.

Here, on the extreme left flank, Bennigsen spoke a lot and passionately and made, as it seemed to Pierre, an important military order. There was a hill in front of Tuchkov’s troops. This hill was not occupied by troops. Bennigsen loudly criticized this mistake, saying that it was crazy to leave the height commanding the area unoccupied and place troops under it. Some generals expressed the same opinion. One in particular spoke with military fervor about the fact that they were put here for slaughter. Bennigsen ordered in his name to move the troops to the heights.

This order on the left flank made Pierre even more doubtful of his ability to understand military affairs. Listening to Bennigsen and the generals condemning the position of the troops under the mountain, Pierre fully understood them and shared their opinion; but precisely because of this, he could not understand how the one who placed them here under the mountain could make such an obvious and gross mistake.

Pierre did not know that these troops were not placed to defend the position, as Bennigsen thought, but were placed in a hidden place for an ambush, that is, in order to be unnoticed and suddenly attack the advancing enemy. Bennigsen did not know this and moved the troops forward for special reasons without telling the commander-in-chief about it.

On this clear August evening on the 25th, Prince Andrei lay leaning on his arm in a broken barn in the village of Knyazkova, on the edge of his regiment’s location. Through the hole in the broken wall, he looked at a strip of thirty-year-old birch trees with their lower branches cut off running along the fence, at an arable land with stacks of oats broken on it, and at bushes through which the smoke of fires—soldiers’ kitchens—could be seen.

No matter how cramped and no one needed and no matter how difficult his life now seemed to Prince Andrei, he, just like seven years ago at Austerlitz on the eve of the battle, felt agitated and irritated.

Orders for tomorrow's battle were given and received by him. There was nothing else he could do. But the simplest, clearest thoughts and therefore terrible thoughts did not leave him alone. He knew that tomorrow's battle was going to be the most terrible of all those in which he participated, and the possibility of death for the first time in his life, without any regard to everyday life, without consideration of how it would affect others, but only according to in relation to himself, to his soul, with vividness, almost with certainty, simply and horribly, it presented itself to him. And from the height of this idea, everything that had previously tormented and occupied him was suddenly illuminated by a cold white light, without shadows, without perspective, without distinction of outlines. His whole life seemed to him like a magic lantern, into which he looked for a long time through glass and under artificial lighting. Now he suddenly saw, without glass, in bright daylight, these poorly painted pictures. “Yes, yes, these are the false images that worried and delighted and tormented me,” he said to himself, turning over in his imagination the main pictures of his magic lantern of life, now looking at them in this cold white light of day - a clear thought of death. “Here they are, these crudely painted figures that seemed to be something beautiful and mysterious. Glory, public good, love for a woman, the fatherland itself - how great these pictures seemed to me, what deep meaning they seemed filled with! And all this is so simple, pale and rough in the cold white light of that morning, which I feel is rising for me. Three major sorrows of his life in particular occupied his attention. His love for a woman, the death of his father and the French invasion that captured half of Russia. "Love. This girl seemed to me full of mysterious powers. How I loved her! I made poetic plans about love, about happiness with it. Oh dear boy! – he said out loud angrily. - Of course! I believed in some kind of ideal love, which was supposed to remain faithful to me during the whole year of my absence! Like the tender dove of a fable, she was to wither away in separation from me. And all this is much simpler... All this is terribly simple, disgusting!

Sinusoidal cells (endothelial cells, Kupffer cells, stellate and pit cells) together with the area of hepatocytes facing the lumen of the sinusoid form a functional and histological unit.

Endothelial cells line the sinusoids and contain fenestrae, forming a stepped barrier between the sinusoid and the space of Disse. Kupffer cells are attached to the endothelium.

Stellate cells livers are located in the space of Disse between hepatocytes and endothelial cells. Disse space contains tissue fluid that flows further into the lymphatic vessels of the portal zones. With an increase in sinusoidal pressure, the production of lymph in the space of Disse increases, which plays a role in the formation of ascites when the venous outflow from the liver is impaired.

The Kupffer cell contains specific membrane receptors for ligands, including the Fc fragment of immunoglobulin and complement component C3b, which play an important role in antigen presentation.

Kupffer cells are activated during generalized infections or trauma. They specifically absorb endotoxin and in response produce a number of factors, such as tumor necrosis factor, interleukins, collagenase and lysosomal hydrolases. These factors increase the feeling of discomfort and malaise. The toxic effect of endotoxin is thus due to the secretion products of Kupffer cells, since it itself is non-toxic.

The Kupffer cell also secretes metabolites of arachidonic acid, including prostaglandins.

The Kupffer cell has specific membrane receptors for insulin, glucagon and lipoproteins. The carbohydrate receptor for N-acetylglycosamine, mannose and galactose may mediate the pinocytosis of some glycoproteins, especially lysosomal hydrolases. In addition, it mediates the uptake of immune complexes containing IgM.

In the fetal liver, Kupffer cells perform erythroblastoid function. Recognition and rate of endocytosis by Kupffer cells depend on otopsonins, plasma fibronectin, immunoglobulins and tuftsin, a natural immunomodulatory peptide. These “liver sieves” filter macromolecules of various sizes. Large, triglyceride-rich chylomicrons do not pass through them, and smaller, triglyceride-poor, but cholesterol- and retinol-rich residues can penetrate into the space of Disse. Endothelial cells vary somewhat depending on their location in the lobule. Scanning electron microscopy shows that the number of fenestrae can be significantly reduced with the formation of a basement membrane; These changes are especially pronounced in zone 3 in patients with alcoholism.

Sinusoidal endothelial cells actively remove macromolecules and small particles from the circulation via receptor-mediated endocytosis. They carry surface receptors for hyaluronic acid (the main polysaccharide component of connective tissue), chondroitin sulfate and a glycoprotein containing mannose at the end, as well as type II and III receptors for FcIgG fragments and a receptor for lipopolysaccharide binding protein. Endothelial cells perform a cleansing function, removing enzymes that damage tissue and pathogenic factors (including microorganisms). In addition, they cleanse the blood of destroyed collagen and bind and absorb lipoproteins.

Liver stellate cells(fat-storing cells, lipocytes, Ito cells). These cells are located in the subendothelial space of Disse. They contain long extensions of cytoplasm, some of which are in close contact with parenchymal cells, and others reach several sinusoids, where they may participate in the regulation of blood flow and thus influence portal hypertension. In a normal liver, these cells are the main storage site for retinoids; morphologically this manifests itself as fat droplets in the cytoplasm. After releasing these droplets, the stellate cells become similar to fibroblasts. They contain actin and myosin and contract when exposed to endothelin-1 and substance P. When hepatocytes are damaged, stellate cells lose fat droplets, proliferate, migrate to zone 3, acquire a phenotype resembling that of myofibroblasts, and produce collagen types I, III and IV, and also laminin. In addition, they secrete cell matrix proteinases and their inhibitors, such as tissue inhibitor of metalloproteinases (see Chapter 19). Collagenization of the space of Disse leads to a decrease in the entry of protein-bound substrates into the hepatocyte.

Pit cells. These are very mobile lymphocytes - natural killer cells, attached to the endothelial surface facing the lumen of the sinusoid. Their microvilli or pseudopodia penetrate the endothelial lining, connecting with the microvilli of parenchymal cells in the space of Disse. These cells do not live long and are renewed by circulating lymphocytes that differentiate in the sinusoids. They contain characteristic granules and vesicles with rods in the center. Pit cells have spontaneous cytotoxicity towards tumor and virus-infected hepatocytes.

Sinusoidal Cell Interactions

A complex interaction occurs between Kupffer cells and endothelial cells, as well as between sinusoid cells and hepatocytes. Activation of Kupferalipopolysaccharides inhibits the uptake of hyaluronic acid by endothelial cells. This effect is possibly mediated by leukotrienes. Cytokines produced by sinusoid cells can both stimulate and suppress the proliferation of hepatocytes.

Could perisinusoidal cells be regional stem cells of the liver? Stellate cells Stellate cells

Links:

Random drawing

Studying the influence of liver Ito cells on stem cells

Experimental assessment of osteoinductivity of recombinant bone morphogenetic protein

Cellular technologies in the treatment of degenerative diseases of bones and joints

Ito cage

Liver cells

About the structure and types of liver lobules

Other types of liver cells and their purpose

The process of interaction of organ elements

About the treatment of organ pathology

Who said that it is impossible to cure severe liver diseases?

Read also:

ENDOTHELIAL CELLS, KUPFER CELLS AND ITO

ENDOTHELIAL CELLS

KUPFER CELLS

ITO CELLS

Psychology and psychotherapy

Ito liver cells

LIVER

Functions.

Structure.

Portal triad and acini.

Liver cells

Ito cage

Story

see also

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Notes

Excerpt characterizing Ito's Cell