Distribution of the VLA family of integrins in normal and pathological human liver tissue

Abstract

The "very late activation" (VLA) subgroup of the integrin superfamily of adhesion molecules plays a central role in cell-cell and cell-matrix interactions. The six different VLA dimers known so far consist of a common beta subunit and a variable alpha (1 to 6) subunit. They serve as receptors for laminin, collagen, and fibronectin or function as adhesion molecules for leukocytes and are therefore of great significance in embryogenesis, growth and repair, and in leukocyte recirculation. The distribution of the common beta and the variable alpha chains of the VLA were studied in normal, inflammatory, and cholestatic liver biopsy samples. In normal liver tissue, vascular endothelia express alpha 1, 2, 3, 5, and 6; bile duct epithelium alpha 2, 3, 5, and 6; connective tissue stroma alpha 1 and 2; hepatocytes alpha 1 and 5; sinusoidal lining cells alpha 1, 2, and 5; and mononuclear cells alpha 4. Whereas bile ducts and vascular endothelia do not show relevant changes in alpha chain expression in liver diseases, hepatocytes de novo express membranous alpha 3 and 6 in inflammatory liver diseases. In view of the role of the VLA-3 and VLA-6 as laminin receptors, this finding is in line with the production of laminin in active liver disease. Moreover, de novo expression of "bile duct type" alpha 2, 3, and 6 on periportal hepatocytes in cholestatic liver disease likely illustrates a phenotypic switch of hepatocytes towards bile duct epithelium during cholestasis.