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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intercellular adhesion molecule-1, an immunoglobulin supergene family member, is known to account for important steps in cell activation and the immune response. By a non-isotopic slot-dot immunoblotting assay, we measured circulating levels of intercellular adhesion molecule-1 in 26 patients with hepatitis C virus-associated chronic active liver disease before and after beta-interferon therapy, in 6 patients with non-A, non-B acute self-limiting hepatitis and in 13 healthy subjects. Circulating intercellular adhesion molecule-1 was found in 10 of 13 (77%) normal controls at low concentrations which were not statistically different from those measured in patients with hepatitis C virus-associated chronic active liver disease responsive to beta-interferon, whereas significantly higher levels were found in unresponsive patients. Higher serum intercellular adhesion molecule-1 levels were found in 4 of 10 (40%) beta-interferon-responsive patients compared with 13 of 16 (18%) unresponsive patients. Intercellular adhesion molecule-1 levels persisted after discontinuation of beta-interferon treatment and did not correlate with hepatocytolysis (as indicated by alanine aminotransferase serum activity) either in chronic active liver disease or acute hepatitis. However, a good correlation was found between intercellular adhesion molecule-1 and its expression on liver cells, thus emphasizing that induced circulating levels may reflect the state of activation at the sites of the inflammatory process. These data strongly support the view that intercellular adhesion molecule-1 plays an important role in liver cell damage in hepatitis C virus-associated acute and chronic liver disease, and that its circulating levels may be a good prognostic parameter of responsiveness to beta-interferon therapy.
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PMID:Circulating levels and liver tissue distribution of intercellular adhesion molecule-1 during beta-interferon therapy of hepatitis C virus-associated chronic active liver disease. 135 8

Using monoclonal antibodies and in situ immunohistochemistry, we studied the distribution of "accessory" adhesion molecules (i.e., intercellular adhesion molecule-1 and leukocyte function-associated antigen-3) in 114 liver biopsy specimens with various inflammatory liver diseases and in 12 control liver biopsy samples without inflammation. The distribution of these adhesion molecules was compared with the presence on inflammatory cells of their natural ligands, lymphocyte function-associated antigen-1 and cluster of differentiation antigen-2, respectively. In normal liver, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 reacted weakly with sinusoidal lining cells, portal vessel endothelium and scattered mononuclear inflammatory cells, whereas hepatocytes were constantly negative. In contrast, all 114 biopsy samples of acute or chronic liver diseases revealed strong expression of intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 on sinusoidal lining cells and on hepatocytes in areas of inflammation. Hepatocellular membrane positivity resulted in a "honeycomb pattern" of staining , which was panacinar in acute hepatitis and focal in chronic persistent or aggressive hepatitis. In various other chronic liver diseases, a multifocal periportal and intraacinar honeycomb pattern was detected. In all cases, a close topographical correlation was found between hepatocellular expression of intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 on one hand and the presence of inflammatory cells expressing lymphocyte function-associated antigen-1 and cluster of differentiation antigen-2 on the other.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical study of adhesion molecules in liver inflammation. 237 85

We investigated the effect of inflammatory cytokines on the intercellular adhesion molecule-1 expression on primary cultured murine hepatocytes. Tumor necrosis factor-alpha, interferon-gamma and interleukin-1 alpha up-regulated the intercellular adhesion molecule-1 expression on hepatocytes in a dose-dependent fashion; however, interleukin-6 did not. On the basis of kinetic analysis, the expression level reached a peak 24 hr after stimulation, and both cycloheximide and actinomycin D inhibited the expression. Furthermore, T lymphocytes bind more to interferon-gamma-stimulated hepatocytes than to unstimulated hepatocytes. The binding was dependent on the concentration of interferon-gamma. The binding was also up-regulated by stimulating T lymphocytes with phorbol myristate acetate. Tumor necrosis factor-alpha and interleukin-1 alpha demonstrated the same effect as interferon-gamma, whereas interleukin-6 did not increase T-lymphocyte adhesion to the hepatocytes. The adhesion induced by interferon-gamma or tumor necrosis factor-alpha was inhibited by antibody against either intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1, a ligand for intercellular adhesion molecule-1, but was not inhibited by CD44 antibodies. These results demonstrate that inflammatory lymphokines enhance the T-lymphocyte adhesion to primary cultured hepatocytes by up-regulating the intercellular adhesion molecule-1 expression on the stimulated hepatocytes by activating the de novo pathway. This mechanism may play an important role in the pathogenesis of hepatitis.
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PMID:Inflammatory cytokines up-regulate intercellular adhesion molecule-1 expression on primary cultured mouse hepatocytes and T-lymphocyte adhesion. 790 80

Concanavalin A (Con A) induces T-cell-mediated hepatic injury in vivo, although Con A-stimulated lymphocytes are not cytotoxic to normal hepatocytes in vitro. This contradiction makes the mechanism of Con A-induced hepatitis elusive. In this study, we demonstrate that Con A but not tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), or actinomycin D (ActD) induced the susceptibility of hepatocytes to activated autologous lymphocyte cytotoxicity. Con A sensitized hepatocytes within 30 minutes after the stimulation in a dose-dependent fashion. The cytotoxicity was dose-dependently inhibited by either a Con A ligand, alpha-methyl mannoside, or a perforin inhibitor, concanamycin A (CMA), but not by anti-Fas ligand antiserum. In addition, Con A-treated hepatocytes were not sensitive to autologous activated lymphocytes from a perforin-deficient mouse, while hepatocytes from lpr mice were sensitized by Con A. In fact, Con A did not induce liver injury in perforin-deficient mice within the concentration employed in this study. Therefore, we conclude that the cytotoxicity was mediated through perforin/granzymes but not through the Fas/Fas ligand pathway. The cytotoxicity was inhibited by anti-intercellular adhesion molecule-1 (ICAM-1)/LFA-1 antibodies, but not by anti-VCAM-1/VLA-4 antibodies, both in vitro and in vivo. The cytotoxicity appears to be caused by CD8+ T cells; however, the cytokines from activated CD4+ T cells play a critical role in the pathogenesis of the hepatitis in vivo, because administration of anti-IFN-gamma antibodies inhibited the occurrence of the hepatitis. In conclusion, Con A-induced hepatitis is thought to be dominantly mediated by a perforin-dependent pathway through ICAM-1/LFA-1 interaction.
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PMID:Concanavalin A induces perforin-mediated but not Fas-mediated hepatic injury. 878 46

Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in the pathogenesis of various inflammatory liver disease states, including viral and autoimmune hepatitis as well as liver allograft rejection. Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine known to up-regulate adhesion molecules as well as major histocompatibility complex (MHC) class I expression, and has been demonstrated to be important in the rejection of vascularized organ allografts. The current studies address the effect of TNF-alpha and the role of ICAM-1 expression on liver cell immunogenicity in vitro in mixed lymphocyte hepatocyte culture (MLHC), in vitro in mixed lymphocyte liver nonparenchymal cell culture (MLNPC), in vivo in hepatocyte sponge matrix allografts (HC-SMA), and in vivo in liver nonparenchymal cell sponge matrix allografts (NPC-SMA). Purified allogeneic hepatocytes (HC) and liver nonparenchymal cells (NPC) under naive, unstimulated conditions demonstrated different profiles of MHC antigen and adhesion molecule expression, but both liver cell populations stimulated the proliferation and development of allospecific cytotoxic effectors in vitro and in vivo. Despite significant up-regulation of MHC class I and ICAM-1 on both HC and liver NPCs by in vivo treatment with TNF-alpha, the immunogenicity of TNF-alpha-stimulated liver cells was not appreciably different from naive, unstimulated liver cells. In contrast, ICAM-1-negative HC and NPCs were significantly less immunogenic both in terms of lymphocyte proliferative responses and the generation of allospecific cytolytic effectors. These results suggest that constitutive expression of ICAM-1 enhances the immunogenicity of "donor" liver cells but is not absolutely required to elicit immune responses to allogeneic liver cells. Further studies to determine the role of adhesion molecule expression on trafficking of host immune cells to the liver and the role of adhesion molecule expression by host cells are required to clarify their role in immune responses to liver cells.
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PMID:Effect of tumor necrosis factor alpha and intercellular adhesion molecule-1 expression on immunogenicity of murine liver cells in mice. 969 13

It is well known that females show a greater susceptibility to alcohol-induced liver injury than males. Additionally, females who consume alcohol regularly and have been obese for 10 years or more are at greater risk for both hepatitis and cirrhosis. Female rats on an enteral alcohol protocol exhibit injury more quickly than males, with widespread fatty changes over a larger portion of the liver lobule. Levels of plasma endotoxin, intercellular adhesion molecule-1, free radical adducts, infiltrating neutrophils, and nuclear factor-kappaB are increased about twofold more in livers from female than male rats after enteral alcohol treatment. Estrogen treatment in vivo increases the sensitivity of Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of alcohol-induced liver injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3) or reduction of bacterial endotoxin by sterilization of the gut with antibiotics blocks early inflammation due to alcohol. Similar results have been obtained with anti-tumor necrosis factor-alpha antibody. These findings led to the hypothesis that alcohol-induced liver injury involves increases in circulating endotoxin, leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This idea has been tested using pimonidazole, a nitroimidazole marker, to quantitate hypoxia in downstream pericentral regions of the liver lobule. After chronic enteral alcohol, pimonidazole binding increases twofold. Enteral alcohol also increases free radicals detected with electron spin resonance. Importantly, hepatic hypoxia and radical production detected in bile are decreased by destruction of Kupffer cells with GdCl3. These data are consistent with the hypothesis that Kupffer cells participate in important gender differences in liver injury caused by alcohol.
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PMID:II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. 975 87

High levels of serum-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have been noted in patients with chronic hepatitis C. This study aimed to measure serum levels of sICAM-1 and sVCAM-1 in asymptomatic hepatitis C virus carriers and clarify the clinical significance of measuring soluble forms. Serum levels of sICAM-1 were significantly higher than in healthy controls but serum sVCAM-1 levels did not differ statistically from those in healthy controls. Liver biopsy obtained from 12 asymptomatic hepatitis C virus carriers showed evidence of hepatitis. Estimating sICAM-1 and sVCAM-1 in asymptomatic carriers may be helpful, especially in cases in which liver biopsy is not possible.
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PMID:Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in asymptomatic carriers of hepatitis C virus. 1039 13

Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution. Lymphocyte attachment was inhibited by pretreatment with anti-E-selectin monoclonal antibody (MAb) or anti-VCAM-1 MAb, and expression of E-selectin and VCAM-1 was suppressed by pretreatment with anti-tumor necrosis factor-alpha (TNF-alpha) MAb. Electron microscopically, lymphocytes were trapped by endothelial lamellipodia and traversed the endothelium by diapedesis. These results indicate that lymphocyte adhesion/transmigration preferentially takes place in the sublobular veins in association with TNF-alpha-induced endothelial activation, i.e., E-selectin and VCAM-1 expression and lamellipodia formation.
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PMID:Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice. 1061 32

The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)-induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range. All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.
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PMID:sICAM-1, sCD95 and sCD95L levels in chronic liver diseases of different etiology. 1073 54

Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A treatment. Increases in plasma transaminase levels, which peaked 8 h after injection, were reduced significantly in L-selectin-/-, ICAM-1-/-, and L-selectin/ICAM-1-/- mice compared with wild-type mice. Liver necrosis was more strongly inhibited in ICAM-1-/- mice than in L-selectin-/- mice but was most prominently reduced in L-selectin/ICAM-1-/- mice, in parallel with decreased plasma transaminase levels. The reduced severity of hepatitis in the mutant mice correlated with decreases in numbers of liver CD4+ T cells but not numbers of CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency reduced liver mRNA expression of tumor necrosis factor-alpha, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1alpha mRNA occurred in all mutant mice. These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production.
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PMID:L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury. 1646 40


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