Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However, aberrant expression occurs in cholestatic diseases such as primary biliary cirrhosis. The aim of this work was to assess the effect of cholestasis itself on hepatocyte MHC expression and to determine if immunosuppressive drugs might modulate this expression. Liver fragments taken from six patients with extrahepatic cholestasis and eight control patients were analyzed for MHC expression by direct immunofluorescence. MHC class I expression by hepatocytes was present in six of six cholestatic patients and zero of eight control subjects. Hepatocytes did not express MHC class II in either group. In further studies, cholestasis was induced in rats by ligation-section of the bile duct. Five groups of rats were studied: control, 3-day cholestasis, 5-day cholestasis, 5-day cholestasis plus cyclosporine, and 5-day cholestasis plus corticosteroids. Hepatocyte MHC class I expression was detected by immunofluorescence in bile duct-ligated rats but not in control animals. Flow-cytofluorimetric analysis of isolated hepatocytes showed that the percentage of hepatocytes expressing MHC class I increased from day 0 (9.9%) to days 3 (50.2%) and 5 (82.9%); this hyperexpression was not modified by cyclosporine (79.7%) or corticosteroids (77.9%). The percentage of hepatocytes spontaneously expressing MHC class II was low (0.05%) and was not significantly modified by cholestasis or immunosuppressive drugs. Thus, a nonimmunological factor such as cholestasis is able to modulate MHC expression. The liver may become more vulnerable to immune destruction in the presence of cholestasis, and immunosuppressive treatment has no effect on this phenomenon.
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PMID:Cholestasis induces major histocompatibility complex class I expression in hepatocytes. 155 54

The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post-transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0-3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post-transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.
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PMID:Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection. 225 Jan 95

The distribution of major histocompatibility complex (MHC) class 1 antigens was studied in the liver after transplantation by immunoperoxidase staining for beta-2-microglobulin (beta 2m), a subunit of the class 1 antigen system. Paraffin wax sections were examined from 25 "time zero" biopsy specimens, taken immediately after insertion of the graft, and 87 biopsy specimens taken after transplantation in seven diagnostic categories: acute cellular rejection (n = 22); resolving acute rejection (n = 8); chronic rejection (n = 22); pure cholestasis (n = 14); ischaemia/infarction (n = 5); biliary obstruction (n = 8); massive haemorrhagic necrosis (n = 8). Staining was graded semiquantitatively on a scale of 0-3+ in bile ducts, hepatocytes, sinusoidal lining cells and vascular endothelium. Using the "time zero" biopsy specimens as a baseline for comparison, increased expression of beta 2m was seen in bile ducts, hepatocytes, and endothelial cells after transplantation. These changes were most pronounced in cases of rejection but also occurred in other graft conditions. The degree of hepatocyte and endothelial staining was significantly higher in cases of rejection and massive haemorrhagic necrosis than in the other categories. These findings may have implications for the pathogenesis and diagnosis of rejection of the transplanted liver.
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PMID:Beta-2-microglobulin expression in the liver after liver transplantation. 305 76

Increased expression of major histocompatibility complex (MHC) antigens may occur following liver transplantation. The mechanism by which this occurs is unclear. Postoperative complications may result in cholestasis. We have investigated the possibility that cholestasis may cause increased expression of MHC antigens in the liver. Cholestasis was induced in rat livers by bile duct ligation and transection. Total serum bilirubin rose markedly postoperatively and remained elevated over a period of 21 days. Samples of bile taken from rats were shown to remain sterile during the study period and there was no evidence of viral infection. Liver tissue taken 1, 3, 7, and 21 days postobstruction showed a marked increase in the expression of rat class I MHC antigens but not class II antigens. We suggest that cholestasis itself can induce increased MHC class I antigens in the liver. Therefore, if cholestasis occurs postoperatively in the human liver transplant recipient this might lead to increased expression of human class I MHC antigens and add to the overall cellular immune activity in a rejection reaction, although cholestasis probably cannot initiate rejection.
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PMID:Increased expression of major histocompatibility antigens in the liver as a result of cholestasis. 328 57

Kupffer cell phagocytic function is reduced in the presence of obstructive jaundice. To investigate possible mechanisms we report a study of the rat liver in extrahepatic cholestasis, using light microscopy, immunohistochemistry and electron microscopy, Immunohistochemistry was performed with monoclonal antibodies specific for rat Kupffer cells ED 1, ED 2 and ED 3 and monoclonal antibodies directed against class II antigens of the rat major histocompatibility complex Ox 3 and Ox 6. Extrahepatic cholestasis was produced by bile duct ligation. In bile duct ligated animals light microscopy showed proliferation of bile ductules and an increase in sinusoidal cells. Immunohistochemistry with ED 1, ED 2 and ED 3 demonstrated a marked increase in the number of positive cells, but few of these cells were positive with Ox 3 and Ox 6, whereas the proliferating bile ductules were strongly positive. Electron microscopy revealed two homogeneous granular substances within the sinusoidal lumen and loss of the space of Disse. Despite a reduction in Kupffer cell phagocytic function in obstructive jaundice there is an increase in Kupffer cells, but these cells appear to be in an inactivated state as few express class II antigens on their surface. Furthermore the granular substance within the space of Disse may interfere with function.
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PMID:The Kupffer cell in experimental extrahepatic cholestasis in the rat--a light microscopy, immunohistochemical and electron microscopy study. 354 74

Primary biliary cirrhosis is known as an autoimmune chronic cholestatic disease and characterized by various immunological abnormalities. Especially, the aberrant expression of major histocompatibility complex (MHC) class I antigens on hepatocytes has been considered to have a pivotal role in the pathogenesis and progression of the disease. However, the underlying mechanism of this aberrant expression of MHC class I molecules has not yet been clarified. In the present study we showed that MHC class I immunoreactivities were increased by treatment with chenodeoxycholic acid (CDCA) in the human hepatoma cell line HLE. Moreover, CDCA treatment of the cells increased the steady-state levels of MHC class I mRNA. Since CDCA is one of major constituents of endogenous bile acids in cholestasis, these results suggest that intrahepatic cholestasis, which is almost inevitably associated with PBC, increases both production and surface expression of MHC class I antigens in hepatocytes.
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PMID:Chenodeoxycholic acid-dependent induction of major histocompatibility complex class I mRNA expression in a human hepatoma cell line. 821 76

Hepatocytes normally express few major histocompatibility complex (MHC) class I and no MHC class II molecules, a phenomenon which could explain their low immunogenicity. However, in pathological situations, such as allograft rejection and cholestasis, hepatocytes strongly express MHC class I molecules and their immunogenicity could be different. The aim of this study was to assess the role of MHC expression on the immunogenicity of hepatocytes in vivo. Hepatocytes were obtained from normal and cholestatic DA rats by whole-liver perfusion with EDTA. Cholestasis was induced by ligation-section of the common bile duct. MHC expression on hepatocytes was assessed by cytofluorimetry after labelling with monoclonal antibodies against MHC class I and class II antigens. The percentage of hepatocytes expressing MHC class I was 9.8 +/- 2.2% in normal rats and 77.2 +/- 3.3% in cholestatic rats (P = 2 x 10(-4)); MHC class II expression was present on 1 +/- 0.5% of normal hepatocytes and 0.4% +/- 0.1% of cholestatic hepatocytes (P > 0.05). Lewis rats received a DA or Wistar-Furth heart allograft 7 days after intravenous injection of 2 x 10(7) hepatocytes from normal or cholestatic DA rats. The DA heart allograft was rejected in 6.3 +/- 0.4 days in Lewis controls, 8.8 +/- 1.1 days (N.S.) in Lewis recipients that received normal DA hepatocytes and 17.6 +/- 3.0 days (P = 2 x 10(-4)) in Lewis recipients that received hepatocytes from cholestatic DA rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunogenicity of rat hepatocytes in vivo: effect of cholestasis-induced changes in major histocompatibility complex expression. 822 27

Interleukin-3 treatment of juvenile rhesus monkeys elicits a dose- and time-dependent syndrome that includes urticaria, palpable lymph nodes, splenomegaly, thrombocytopenia, anemia, vomiting, diarrhea, intestinal bleeding, edema, and arthritis, apart from a strong stimulation of hemopoiesis. Arthritis was found to occur significantly more often in animals expressing the major histocompatibility complex alleles B9 and Dr5. Histological analysis revealed an abundance of mast cells in urticaria and, to a lesser extent, in lungs and synovia of arthritic joints. Active osteoclasts were abundant in ribs and arthritic joints. Extramedullary hemopoiesis was encountered in liver, spleen, and kidneys. The spleen showed deposits of hemosiderin, and in the liver, Kupffer cells were loaded with iron, indicating enhanced turnover of hemoglobin. Lymph nodes and bone marrow showed macrophages involved in hemophagocytosis, which probably contributed to the development of anemia and thrombopenia. Biochemical parameters in sera were indicative of parenchymal liver damage, with cholestasis and increased erythrocyte destruction. The side effects were strongly reduced in monkeys subjected to total body irradiation just before interleukin-3 treatment. Histamine antagonists were not significantly effective in preventing side effects, which is explained by the perpetual stimulation of basophilic granulocytes by exogenous interleukin-3. The nature of the side effects indicates that interleukin-3 may be involved in the pathogenesis of acute type hypersensitivity reactions and arthritis.
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PMID:Acute side effects of homologous interleukin-3 in rhesus monkeys. 825 52

Bile duct cells (BDCs), especially intrahepatic cholangiocytes, are primary targets of immune-related injury in such pathologic processes as liver graft rejection, liver graft-versus-host disease, and primary sclerosing cholangitis. Cholestasis and progressive loss of intrahepatic BDCs indicate chronicity in these diseases. The present investigation characterizes the acquisition of immune markers of intrahepatic BDCs isolated from mice after bile duct ligation. Purified BDCs from cholestatic C57BL/6 (H-2b) mice express not only the major histocompatibility complex (MHC) class I and class II antigens but also the costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The expression of the MHC class II molecules on BDCs before and after interferon (IFN)-gamma exposure is also demonstrated by immunohistochemistry on the cultured cells. Cytotoxicity assays indicate the vulnerability of these cells as targets for immunologic injuries. Effector cells generated from B10.BR splenocytes (H-2k) against C57BL/6 splenocytes (H-2b) show comparable killing of BDCs and EL4 cells, the latter being a lymphoma line that was established from the C57BL/6N (H-2b) mouse. An immortalized mouse BDC line (IBDC) is included in this study to validate some of the findings from BDCs isolated from bile duct-ligated mice. We suggest that cholestatic BDCs express surface antigens different from those of normal epithelial cells that result in increased susceptibility to damage by immune mechanisms.
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PMID:Phenotypical and functional characterization of intrahepatic bile duct cells from common duct ligated mice. 896 Jun 34

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are presumed autoimmune chronic cholestatic liver diseases characterized by cholangitis and progressive loss of bile ducts. Cytokines have been postulated to be involved in the progression of these diseases, but their role is poorly defined. Our objectives were to characterize a rat model of cholangitis and to determine Type 1/Type 2 (Th1/Th2) cytokine profile shifts in this model. Cholangitis was induced in Sprague-Dawley rats (200 to 225 g) by low-dose oral administration of the biliary toxin alpha-naphthylisothiocyanate (ANIT) (1 g/kg powdered rat chow ad libitum) for 4, 7, and 14 days. Cholestasis was observed in ANIT-treated animals. Liver histology of ANIT-treated rats showed hepatic inflammation centered on damaged bile ducts, significant bile duct proliferation, and progressive fibrosis. Immunohistochemistry showed enhanced staining of hepatic major histocompatibility complex (MHC) II, CD4, and CD8 in portal areas of ANIT-treated animals. In addition, the hepatic cytokine profile became increasingly Th1 in nature with progressive ANIT treatment. In summary, experimental cholangitis biochemically and histologically mimics human chronic cholangitis and furthermore, is associated with a progressive shift to a more Th1-dominant hepatic cytokine profile. Therefore, this model may be useful for examining the role of cytokines in the progression of chronic cholangitic diseases.
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PMID:Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis. 1065 47


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