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

Meinrad Gawaz, Korbinian Brand, Timm Dickfeld, Gisela Pogatsa-Murray, Sharon Page, Caroline Bogner, Werner Koch, Albert Schömig, Franz Josef Neumann

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

Abstract

Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-1) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with α-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P<0.01) that could be inhibited by interleukin-1 (IL-1) antagonists by approximately 40%. Activation of transcription factor nuclear factor-κB (NF-κB) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-1 mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and κB-dependent transcriptional activity. In trans-well experiments, α-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (α(v)β3) on the luminal aspect of endothelial monolayers and promoted α(v)β3-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-1) and adhesive (surface expression of ICAM-1 and α(v)β3) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.

Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalAtherosclerosis
Volume148
Issue number1
DOIs
StatePublished - Jan 2000

Keywords

  • Atherogenesis
  • Endothelium
  • Intercellular adhesion molecule-1
  • Monocyte chemotactic protein-1
  • Nuclear factor-κB
  • Platelets

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