Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis

Platelets and alterations of chemotactic and adhesive properties of endothe lium play an important role in the pathophysiology of atherosclerosis. We i nvestigated the effect of platelets on secretion of monocyte chemotactic pr otein-1 (MCP-I) and on surface expression of intercellular adhesion molecul e-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers o f endothelial cells with alpha-thrombin-activated platelets significantly e nhanced secretion of MCP-1 and ICAM-1 surface expression (P < 0.01) that co uld be inhibited by interleukin-l (IL-I) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappa B (NF-kappa B) whic h regulates transcription of early inflammatory response genes such as MCP- 1, was significantly increased in endothelial cells treated with activated platelets via an IL-I mediated mechanism as determined by electrophoretic m obility shift assay (EMSA) and kappa B-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1 -dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-m ediated platelet/endothelium adhesion that could be inhibited by the antiad hesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets i nduce significant changes in chemotactic (secretion of MCP-I) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured e ndothelium. These findings imply a potential pathophysiological mechanism o f platelets in an early stage of atherogenesis. (C) 2000 Elsevier Science I reland Ltd. All rights reserved.