Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes

Abstract

SUMMARY A circulating form of the membrane‐bound ICAM‐1 (CD54). a ligand for lymphocyte function‐associated antigen‐1 (LFA‐I), has recently been identified in normal human scrum. In this study. scrum levels of soluble ICAM‐1 (sICAM‐1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC). primary sclerosing cholangitis and chronic active hepatitis (autoimnune) showed significant elevations in sICAM‐1 compared with normal healthy subjects. The median level in PBC was approximately seven‐fold above normal. Significant elevations in sICAM‐1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC. sICAM‐I levels were related to summary assessment of disease severity (Child‐Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E‐selectin did not differ significantly from healthy controis. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM‐I. investigation of ICAM‐I gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM‐1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM‐1 in this disease. Similar increases in ICAM‐I mRNA expression were found in cultured, concanavalin A (Con A)‐stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression ofICAM‐1 and the secretion/shedding of sICAM‐1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may bean important sourceofsICAM‐1 in autoimmune and other chronic liver diseases. The possible role of sICAM‐1 in inflammatory disorders remains to be determined.

Soluble intracellular adhesion molecule, M30 and M65 as serum markers of disease activity and prognosis in cholestatic liver diseases

“…As reviewed by Kremer et al ., there are substantial restrictions for a clinical use of apoptotic markers in peripheral blood such as: (i) absent specificity; (ii) uncertain chronological decline of serum levels/activities; and (iii) competing pathomechanisms of cell death such as necrosis or necroptosis. Nevertheless, there have been attempts to establish apoptotic markers for clinical practice of immune‐mediated liver diseases …”

“…In accordance with previous reports, the apoptotic markers sFas and sICAM (the latter in our study only in PSC) were elevated in sera of patients with immune‐mediated liver diseases when compared with healthy controls reflecting the higher rate of apoptosis under these pathological conditions. sICAM is the soluble form of the cell adhesion molecule ICAM (CD54), that seems to be involved in the pathogenesis of autoimmune hepatitis, and sFas is the soluble form of Fas (CD95), a receptor on the cell surface, that is an inducer of cellular apoptosis…”

Adhesive molecules and inflammatory markers among hepatitis C virus Saudi patients

“…Many previous studies reported increased sICAM-1 and sVCAM-1 values in patients with inflammatory diseases of the liver (34)(35)(36)(37)(38). While, elevated serum VCAM-1 in chronic hepatitis have been reported by some authors (39,40).…”

Serum Levels of Soluble Adhesion Molecules as Prognostic Factors for Acute Liver Failure

“…However, this study indicated that, in ALF patients, lower serum sICAM-1 levels were associated with their fatal outcomes. Part of sICAM-1 has been reported to be secreted from hepatocytes stimulated with pro-inflammatory cytokines such as IFN-γ, IL-1β and TNF-α [35]. After hepatic resection, serum sICAM-1 levels have been shown to decrease [36].…”