the cxc-chemokine cxcl4 interacts with integrins implicated in angiogenesis的cxc-chemokine cxcl4与整合蛋白与血管生成.pdfVIP

The CXC-Chemokine CXCL4 Interacts with Integrins Implicated in Angiogenesis 1,2 1,2 3 1,2 Sallouha Aidoudi *, Kinga Bujakowska , Nelly Kieffer , Andreas Bikfalvi * ´ ´ 1 INSERM, U920, Talence, France, 2 Univ Bordeaux, Talence, France, 3 Laboratoire de Biologie et Physiologie Integree (CNRS/GDRE-ITI), University of Luxembourg, Luxembourg City, Luxembourg Abstract The human CXC-chemokine CXCL4 is a potent inhibitor of tumor-induced angiogenesis. Considering that CXCL4 is sequestered in platelet a-granules and released following platelet activation in the vicinity of vessel wall injury, we tested the hypothesis that CXCL4 might function as a ligand for integrins. Integrins are a family of adhesion receptors that play a crucial role in angiogenesis by regulating early angiogenic processes, such as endothelial cell adhesion and migration. Here, we show that CXCL4 interacts with avb3 on the surface of avb3-CHO. More importantly, human umbilical vein endothelial cells adhere to immobilized CXCL4 through avb3 integrin, and also through other integrins, such as avb5 and a5b1. We further demonstrate that CXCL4-integrin interaction is of functional significance in vitro, since immobilized CXCL4 supported endothelial cell spreading and migration in an integrin-dependent manner. Soluble CXCL4, in turn, inhibits integrin-dependent endothelial cell adhesion and migration. As a whole, our study identifies integrins as novel receptors for CXCL4 that may contribute to its antiangiogenic effect. Citation: Aidoudi