Modulation of extracellular matrix receptors (integrins) on human endothelial cells by cytokines

Abstract

Integrins are a family of receptor proteins that mediate adhesive interactions [1–3]. Human umbilical vein endothelial cells (HEC) express five distinct integrin complexes that mediate their interaction with basal membrane components [4–7]. We found that tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma), two cytokines known to trigger the inflammatory response and to modify the HEC properties [8], induce selective alterations in the integrin expression. While TNFalpha induces the expression of a laminin-collagen receptor (integrin alpha-1/beta-1), not expressed in unstimulated HEC, a combination of TNFalpha and IFNgamma downregulates the vitronectin receptor (integrin alpha-v/beta-3). These modifications require a minimum of 24 h of exposure to cytokines and reach maximal levels between 48 and 72 h. Such alterations change the adhesive properties of the cells in a selective manner since the expression of other integrins (alpha-3/beta-1 and alpha-5/beta-1) are not altered, and are likely to play a role in the late phase of the inflammatory response.