Cell adhesion and integrin expression are modulated by oxidative stress in EA.hy 926 cells

摘要

The effects of oxidative stress on integrin- mediated cell adhesion to the extracellular matrix ( ECM) and related apoptosis were investigated using the EA. hy926 endothelial cells treated ( or not) with two oxidants: the hypoxanthine/xanthine oxidase system (HX/XO) or the tert-butyl hydroperoxide (t-BHP) which both increased cell apoptosis. Cell adhesion onto vitronectin (Vn) and fibronectin (Fn) was increased at low concentrations of HX/XO (up to 5 mU/ml) or t-BHP (up to 125mM) and prevented ROS-induced apoptosis. Flow cytometry analysis of integrin expression showed that the expression of integrin av and alpha 5 subunits was, respectively, increased and decreased. Cell adhesion inhibition experiments using function-blocking monoclonal antibodies against integrin subunits indicated that alpha v beta 1 and alpha v beta 3 integrins were involved in adhesion of cells to Vn, and avb3 integrin played a major role in oxidant-treated cells. For adhesion to Fn, a5b1 and avb1 integrins were required for oxidant-treated cells. Taken together, the results suggest that reactive oxygen species ( ROS) produced either by HX/ XO or t-BHP could affect expression and/or activation of specific integrins in the interaction of EA.hy926 cells with ECM.