Distribution of basement membrane proteins in normal and fibrotic human liver: Collagen type IV, laminin, and fibronectin

Abstract

Specific antibodies to collagen type IV, laminin, and fibronectin were used to localize these proteins by indirect immunofluorescence in frozen sections of normal and fibrotic liver. In normal livers distinct staining was found in basement membranes of blood and lymph vessels, of bile ducts and ductules and around nerve axons. Positive reactions for type IV collagen and fibronectin were also observed in the perisinusoidal space, while hepatocytes and most of the interstitial matrix of portal fields, remained unstained. Liver specimens obtained from patients with alcoholic liver disease (fatty liver, hepatitis or cirrhosis) and chronic active hepatitis showed a more intense reaction with the antibodies in the perisinusoidal space including now distinct staining for laminin. These patterns were particularly prominent at borders between fibrotic septa and remnants of parenchyma or pseudolobules. Strong reactions were also found for type IV collagen and fibronectin in the periportal interstitium and in large fibrotic areas. The findings support previous electron microscopical and chemical evidence for increased basement membrane production in human liver fibrosis and demonstrate that this may involve different proteins and occur at different anatomical sites.