Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: Relationship with disease stage, immune activity and cholestasis

Abstract

Intercellular adhesion molecule-1, strongly expressed on the interlobular and proliferating bile ducts in primary biliary cirrhosis, is important in the migration and adhesion of inflammatory cells from the circulation to these structures. A soluble form has been found to be elevated in serum in primary biliary cirrhosis. Our aim was to check on the role of soluble intercellular adhesion molecule-1 in primary biliary cirrhosis with particular reference to its specificity by comparison with other disease control groups and to assess its relationship with stage of disease activity, circulating lymphocyte activation and cholestasis. Soluble intercellular adhesion molecule-1 (enzyme-linked immunosorbent assay) and liver biochemistry were measured in 41 patients with primary biliary cirrhosis, 9 with primary sclerosing cholangitis, 12 with alcoholic liver disease and 17 healthy controls. In subgroups of patients with primary biliary cirrhosis, lymphocyte activation and hepatic bile acid uptake and excretory rates were determined. Soluble intercellular adhesion molecule-1 was significantly higher in all three disease groups. Levels in primary biliary cirrhosis and primary sclerosing cholangitis were similar and significantly higher than alcoholic liver disease. Soluble intercellular adhesion molecule-1 expression was greater in late primary biliary cirrhosis than early disease and correlated with histological progression. Correlations were also found with alkaline phosphatase, gamma-glutamyl transpeptidase and conjugated bilirubin. A trend toward an inverse correlation with hepatic excretory rate was found, but no correlation was detected with circulating lymphocyte interleukin-2 receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence of an increased nitric oxide production in primary biliary cirrhosis

“…In agreement with previous reports (28,29), we have found that serum concentrations of soluble forms of ICAM-1 and E-selectin are significantly elevated in PBC patients relative to normal subjects. Although similar to levels measured in CH subjects, in PBC they are highly increased as compared to those detected in cirrhotic patients.…”

“…This may reflect upregulated expression of adhesion molecules on bile ducts, hepatocytes, vascular endothelial cells, and infiltrating leukocytes, a critical step in the pathogenesis of immunemediated destruction of interlobular bile ducts and hepatocytes (3,6). Although not specific to PBC, increased serum levels of circulating forms of adhesion molecules have been correlated with the stage of progression of the disease (9,10,29). Indeed, this is supported by relationships between soluble adhesion molecules and biochemical markers of cholestasis in our study.…”

Release of soluble intercellular adhesion molecule 1 into bile and serum in murine endotoxin shock

“…Adams et al hy-and secretion of an alternatively spliced form of ICAM-1 as a possibility 22 or the general shedding/cleavage of pothesized that sICAM-1 may be derived from activated lymphocytes accumulated in the liver, 23 however, the extracellular domain of ICAM-1 from the surface of parenchymal cells and vascular endothelial cells in lymphocyte activation does not always correlate with serum levels of sICAM-1. 26 Moreover, in our experi-the liver and extrahepatic tissue. [28][29][30][35][36][37] The latter mechanism is unlikely the result of cell injury because mental model, neutrophils and not lymphocytes are the cytotoxic cell type in the liver 3 suggesting that liver the highest serum levels and biliary efflux rates were measured without liver injury and even in the galactoscells other than lymphocytes have to be the source of sICAM-1.…”

“…22 Subsequent investigations indicated that plasma levels of sICAM-1 are elevated in most inflamAbbreviations: ICAM-1, intercellular adhesion molecule 1; mRNA, messenger RNA; sICAM-1, soluble ICAM-1; PBS, phosphate-buffered saline; TNF-a, matory liver diseases in humans. [23][24][25][26] The hypothesis tumor necrosis factor a; IL-1, interleukin-1.…”

“…26 Moreover, in vitro stud-induced liver injury, 3 where ICAM-1 mRNA induction and the beneficial effect of an anti-ICAM-1 antibody were shown in vivo. 8 Endotoxin and galactosamine were dissolved in sterile phos-(C) are compared with animals treated with 100 mg/kg Salmonella phate-buffered saline (PBS) (pH 7.0).…”