title: Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells.
abstract: BACKGROUND
  Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed.
  
  
  RESULTS
  Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05).
  
  
  CONCLUSIONS
  The present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism. Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis.
authors.affiliation: Medizinische Klinik und Deutsches Herzzentrum and Institut für klinische Chemie und Pathobiologie, Klinikum rechts der Isar der Technischen Universität München, Germany. gawaz@dhm.mhn.de
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: F J
authors.initials: FJ
authors.lastname: Neumann
authors.forename: T
authors.initials: T
authors.lastname: Dickfeld
authors.forename: W
authors.initials: W
authors.lastname: Koch
authors.forename: K L
authors.initials: KL
authors.lastname: Laugwitz
authors.forename: H
authors.initials: H
authors.lastname: Adelsberger
authors.forename: K
authors.initials: K
authors.lastname: Langenbrink
authors.forename: S
authors.initials: S
authors.lastname: Page
authors.forename: D
authors.initials: D
authors.lastname: Neumeier
authors.forename: A
authors.initials: A
authors.lastname: Schömig
authors.forename: K
authors.initials: K
authors.lastname: Brand
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology* / Q000628:therapy; D001792:Blood Platelets / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology*; D015539:Platelet Activation; D011401:Promoter Regions, Genetic
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1