Angiogenesis induced by adhesion between polymorphonuclear leukocyte and endothelial cell via intercellular adhesion molecule-1

Abstract

We demonstrate that adhesion between polymorphonuclear leukocyte (PMN) and endothelial cells (ECs) is concerned with induction of angiogenesis of ECs. For the tube formation assay, ECs obtaine from bovine thoracic aorta (BAECs) grown on a layer of collagen type I were used. Addition of PMNs treated with N-formyl-methionyl-leucy phenylalanine (FMLP), a selective activator of PMN induced angiogenesis The angiogenesis was blocked by monoclonal antibodies against E-selectin and intercellular adhesion molecule-1 (ICAM-1) which inhibit the adhesion between PMN and EC. Ets-1, which stimulates metalloproteinase gene transcription or integrin s3, has a key role in angiogenesis. Addition of activate PMNs to ECs stimulated the angiogenesis and Ets-1 expression. Both the angiogenesis and the Ets-1 expression induced by PMNs were reduced by ets-1 antisense oligonucleotide. On the other hand, PMN-induced Ets-1 expression was reduced by a monoclonal antibody against ICAM-1 but not E-selectin despite the inhibition of PMN-induced angiogenesis by both antibodies. The enhancement of angiogenesis by FMLP-treated PMNs Was blocked by catalase, a scavenging enzyme of H2O2, but not by superoxide dismutase (SOD). Interestingly, the stimulation of angiogenesis by H2O2 without PMNs was inhibited by anti E-selectin antibody but not anti ICA1V 1. ICAM-1 stimulation occurred by ICAM-1 cross-linking enhanced angio genesis. These findings indicated that PMN adhesion was related with the induction of angiogenesis, and ICAM-1 in endothelial cells acted as a signaing receptor to induce Ets-1 expression, whereas E-selectin seemed to function in the formation of tube-like structures in vascular endothelial cell cultures.