Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver.

Abstract

The subendothelial space of normal rat liver contains the constituent proteins of a basal lamina, as judged by immunohistochemical study of tissue sections. However, it is unknown whether these proteins constitute a complex with effects on hepatocellular function. We have examined this question, using normal rat hepatocytes cultured on substrata of matrix proteins as a model of the interaction between cells and basal lamina in vivo. In cultures on a type I collagen substratum, albumin secretion decreased progressively after 2 d. By contrast, when cells were cultured on a laminin-rich gel matrix, albumin secretion was stable for at least 3 wk; other functions and ultrastructural morphology were similarly maintained. None of the individual matrix proteins effectively substituted for the gel matrix, suggesting that full support of hepatocellular function requires a complex of matrix proteins. We speculate that a cause of hepatocellular dysfunction in acute inflammation is disruption of this matrix and alteration of its interaction with the hepatocyte plasma membrane.