The hepatic extracellular matrix. I. Electron immunohistochemical studies in normal rat liver

Monospecific antibodies directed against fibronectin, type I collagen, and two basement membrane components, laminin and type IV collagen, were localized in normal rat liver by light and electron microscopy immunohistochemistry. Type I collagen was found in the liver capsule, protal stroma, and in Disse's space where it was often in direct contact with the hepatocyte plasmalemma; along the sinusoidal wall, type I collagen was more abundant at points of branching or inflexion. Collagen type IV was found in all basement membranes: ductal, neural, and vascular. In addition, small, discrete, discontinuous, deposits of type IV collagen were found along the entire length of the sinusoid. Laminin codistributed with type IV collagen in all basement membranes but was not found in the sinusoidal wall. The structural glycoprotein, fibronectin, was found in the liver capsule and portal stroma but not in basement membranes. However, fibronectin was found in direct contact with the hepatocytes microvilli forming an almost continuous structure; it was the most prominent component of the extracellular matrix in Disse's space. These findings provide a new image of the Disse's space. Rather than being an empty space, as suggested by classic electron microscopy, it was found to contain an extracellular matrix with several unique features: type I collagen, in direct contact with hepatocytes and endothelial cells, formed the scaffold of the hepatic lobule. Type IV collagen was found "free," not associated with laminin and not forming part of a basement membrane. Hepatocytes and endothelial cells lacked a basement membrane but were separated by an extracellular matrix containing predominantly fibronectin, some type I collagen, and occasional spotty deposits of type IV collagen. Future studies of the physiology and pathology of the hepatic sinusoid will have to take into account this unique extracellular matrix.