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 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 alpha-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-kappaB (NF-kappaB) 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 kappaB-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)-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 alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.
Gawaz
M
M
Medizinische Klinik and Deutsches Herzzentrum and Institut für Klinische Chemie und Pathobiochemie, Klinikum Rechts der Isar, Technische Universität München, Lazarettstrasse 36, 80636, Munich, Germany.
Brand
K
K
Dickfeld
T
T
Pogatsa-Murray
G
G
Page
S
S
Bogner
C
C
Koch
W
W
Schömig
A
A
Neumann
F
F
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D019030:Receptors, Vitronectin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D018932:Chemokine CCL2; D007375:Interleukin-1; D016328:NF-kappa B; D019030:Receptors, Vitronectin; D018799:Intercellular Adhesion Molecule-1; D013917:Thrombin