Modulation of alpha(1)beta(1) integrin mediated adhesion of hepatocytes tocollagen IV and laminin by divalent cations

Cell matrix interactions play a critical role in hepatic development and re generation after acute injury. These interactions are mediated by transmemb rane receptors belonging mainly to the integrin family. We have tried to as sess the role of divalent cations in mediating attachment of hepatocytes to matrix proteins like collagen IV (Col IV) and laminin (Ln). The three cati ons examined viz. Ca2+, Mg2+ and Mn2+ showed attachment promoting activity. Since alpha (1)beta (1) integrin is a common receptor for col IV and LN in liver, the effect of cations in its binding to these matrix proteins was s tudied. Although cations in general enhanced the binding, different cations exhibited differential effect in promoting the binding for different ligan ds. Mg2+ ions were more effective in promoting the binding of alpha (1)beta (1) integrin to col IV but Ca2+ proved to be more effective one for Ln. Ki netic analysis of binding in dot blot assays using different concentrations of cations showed that while Mg2+ was active at low concentrations Ca2+ an d Mn2+ promoted the binding more at higher concentrations. Absence of compe titive effect in binding studies showed that they bind at different sites o n the receptor. Differential effects of cations in promoting the binding of alpha (1)beta (1) integrin to CoI IV and Ln suggest that changes in level of diffusible cations can modulate affinity of the common receptor alpha (1 )beta (1) integrin to its ligands and can influence adhesion of hepatic cel ls to different matrix proteins during hepatic development and regeneration .