REGULATION AND FUNCTION OF AN ACTIVATION-DEPENDENT EPITOPE OF THE BETA-1 INTEGRINS IN VASCULAR CELLS AFTER BALLOON INJURY IN BABOON ARTERIES AND IN-VITRO

Migration aad proliferation of endothelial cells (ECs) and smooth musc le cells (SMCs) contribute to the response to injury in damaged and at herosclerotic vessels, These events might be regulated by cellular int eractions with extracellular matrix through the expression and activat ion of integrins To study the functions of beta 1 integrins in the ves sel wall, we used monoclonal antibody (MAb) 15/7, which recognizes an activation epitope of beta 1 integrin subunits, and MAb 8A2, which ind uces a high affinity form of beta 1 integrins recognized by MAb 15/7, Immunohistochemical analyses were done on samples of normal baboon sap henous arteries and from arteries subjected to balloon injury. EC and SMC expressed the activation epitope of beta 1 integrin in uninjured a rteries. By, contrast, in balloon-induced arteries 6 weeks after injur y, regenerating EC did not express the activation epitope, and there w as no decrease in the expression of total beta 1 integrin, whereas SMC migrating into the intima exhibited decreased expression of the total and activated beta 1 integrin. Flow cytometer analysis of cultured ce lls indicated that baboon EC and SMC weakly express the activation epi tope of beta 1 integrin. Next, we determined by utilizing MAb 8A2 the effects of increased expression of activation epitope of beta 1 integr in on the functions of SMC and EC. The activation of beta 1 integrins on SMC induced by MAb 8A2 enhanced SMC adhersion and suppressed SMC mi gration in a Boyden chamber assay, SMC proliferation was inhibited by MAb 8A2 dose-dependently. Similarly, MAb 8A2-induced activation of bet a 1 integrins on EC suppressed EC migration into a wound. However, MAb 8A2 did not affect the basic fibroblast growth factor-induced prolife ration of Ec, at though it blocked the decrease in EC number caused by the removal of basic fibroblast growth factor, These results suggest that activation of beta 1 integrins in vascular cells is regulated in a cell type dependent manner and plays an important role in modulating vascular cell functions.