Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells.
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.
Gawaz
M
M
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
Neumann
F J
FJ
Dickfeld
T
T
Koch
W
W
Laugwitz
K L
KL
Adelsberger
H
H
Langenbrink
K
K
Page
S
S
Neumeier
D
D
Schömig
A
A
Brand
K
K
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
D018932:Chemokine CCL2; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1