Studies on the intercellular adhesion of rat and chicken hepatocytes. Conditions affecting cell-cell specificity.

Abstract

We have previously reported that hepatocytes isolated from young rats and chickens show marked adhesive specificity.That is, when suspensions of hepatocytes from both species are mixed, the cells adhere preferentially to homologous rather than to heterologous cells.The present studies were designed to extend these observations by investigating more definitively the conditions required for specific intercellular adhesion, in particular by examining the effects of different sera and divalent cations.In serum-free medium, adhesive specificity was displayed by the hepatocytes in the absence of divalent cations or in the presence of M8+.In the presence of Ca2+, however, the cells adhered in a random manner (adhesive nonspecificity).This calcium-dependent nonspecificity was reversed when serum, particularly chicken serum, was added to the medium.Evidence is presented t h a t the calcium-induced nonspecificity is mediated by the rat hepatic asialoglycoprotein binding protein (Ashwell, G., and Morell, A. G. (1974) Adu.En-zymoL Relat.Afeas Mol.BioL 41, 99-128) and galactosyl-terminated glycoproteins and/or glycolipids on the surfaces of the chicken hepatocytes.Adhesive specificity was restored, however, in Ca2+-containing serumfree medium when galactose-terminated glycoproteins were added to inhibit the hepatic binding protein activity.In addition, these galactose-terminated glycoproteins did not affect the rate of homologous cell adhesion.These results indicate that the hepatic binding proteins are not normally involved in intercellular adhesion.Confirmation of this conclusion was obtained by studies with antibodies directed against the purified chicken hepatic agalactoglycoprotein binding protein.With concentrations of antibody which completely blocked the uptake of N-acetylglucosamine-terminated