The Role of VCAM-1 in the Pathogenesis of Hepatitis-C-Associated Mixed Cryoglobulinemia Vasculitis
The pathogenesis of the vasculitic lesions due to hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) involves leukocyte adhesion to endothelial cells. We have studied the three endothelial adhesion molecules primarily involved in leuko-endothelial adhesion, namely ICAM-1, VCAM-1, and ELAM-1. Soluble VCAM-1 was found in high concentrations in the serum of HCV-MC patients while in nerve biopsies from HCV-MC patients with more severe forms of the disease VCAM-1 was detected in the perineural vessels. In vitro stimulation of human umbilical vein endothelial cells with cryoprecipitates purified from HCV-MC serum mainly induced the expression of VCAM-1 and ELAM-1 expression on the endothelial cell surface, in a mechanism likely to involve C1q, which was detected in all cryoprecipitates. Thus, in agreement with recent of a role for VCAM-1 in several animal models of immune-complex-mediated-diseases, these data suggest that VCAM-1 is involved in the pathogenesis of HCV-MC vasculitis.
KeywordsHuman Umbilical Vein Endothelial Cell Adhesion Molecule Expression Nerve Biopsy Mixed Cryoglobulinemia Cremaster Muscle
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