The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis

Abstract

Monospecific antibodies against collagen types I, IV, fibronectin, and laminin were used to characterize the hepatic extracellular matrix in CCl4-induced cirrhosis. Of the four antigens studied, fibronectin was the first (2 weeks) to be deposited in Disse's space. Synthesis of fibronectin by hepatocytes was demonstrable by 3 weeks. This increased synthesis and deposition of fibronectin continued throughout the cirrhotic process. Type I collagen was deposited in the same areas as fibronectin, but there was a delay of 2 weeks between fibronectin deposition and the subsequent type I collagen deposition. Like fibronectin, type I collagen was localized in the rough endoplasmic reticulum of hepatocytes, but unlike fibronectin type I collagen synthesis was restricted to hepatocytes near zones of necrosis. Type I collagen and fibronectin synthesis were demonstrable only in hepatocytes. Type IV collagen deposition was noticeable after 3 to 4 weeks of CCl4 administration and continued throughout the cirrhotic process. Laminin deposition was delayed, with regard to type IV collagen, by 1 to 2 weeks. Except for this time lag, both basement membrane components codistributed in the space of Disse and were synthesized by the same cells: endothelial, smooth muscle, and Ito cells. The deposition of these two basement membrane components culminated with the formation of continuous endothelial basement membranes. The four extracellular matrix components studied were synthesized and secreted by resident cells of the normal liver. It is proposed that fibronectin deposition in the space of Disse, modulating collagen deposition, may be the crucial event in the cirrhotic process. The interposition of basement membranes between plasma and hepatocytes may have profound effects on hepatic systemic functions.