The involvement of integrin alphavbeta3 in polymorphonuclear leukocyte-induced angiogenesis in bovine aortic endothelial cells

We have previously reported that angiogenesis stimulated by adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells (ECs) via intercellular adhesion molecule-1 (ICAM-1) might be mediated by a transcription factor, ets-1, which regulates adhesion molecules such as integrins related to angiogenesis. However, the regulation mechanisms of PMN-induced angiogenesis mediated by ICAM-1 remain unclear. Therefore, we investigated the effects of PMN on EC attachment to the extracellular matrix (ECM), which is one of the critical elements for angiogenesis development. After the addition of PMNs, attachment of bovine aortic endothelial cells (BAECs) to vitronectin, which is known as a ligand for integrin alpha(v)beta(3), increased greatly. Stimulation of BAEC with PMN induced expressions of integrin beta(3) mRNA and protein. PMN-induced angiogenesis was inhibited by Arg-Gly-Asp (RGD) peptide and LM609 anti-alpha(v)beta(3) antibody. The PMN-induced BAEC attachment to vitronectin was inhibited by ets-1 antisense oligonucleotide and anti-ICAM-1 antibody. These results suggested that enhancement of EC attachment to ECM via integrin alpha(v)beta(3) participated in the development of PMN-induced angiogenesis. Furthermore, the increase in EC attachment to ECM by ligation of PMN to ICAM-1 might be regulated by Ets-1 expression.