Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8.
Platelet factor 4 (PF-4), a member of the CXC-subfamily of chemokines, is secreted in high amounts by activated platelets. In previous studies, we found that PF-4 specifically binds to human polymorphonuclear granulocytes (PMN), but requires tumor necrosis factor-alpha (TNF-alpha) as a costimulus for the induction of effector functions in suspended cells. In the present study, we have examined PF-4 in comparison with interleukin-8 (IL-8) for its ability to promote interaction of PMN with cultured endothelial cells (EC). We show here for the first time that PF-4 dose-dependently induces PMN to undergo extremely firm adhesion to EC as well as to exocytose secondary granule contents in the presence of these cells. Interestingly, costimulation by TNF-alpha was not required, indicating that EC could provide a corresponding signal(s). As evident from antibody blocking experiments, PF-4-induced adhesion involved PMN-expressed L-selectin as well as leukocyte function-associated molecule-1 (LFA-1), whereas IL-8 involved MAC-1. Because blocking antibodies to LFA-1 but not to L-selectin or MAC-1 abrogated PF-4-dependent marker exocytosis from PMN, the costimulatory signal provided by EC appears to be elicited through cell-cell contact via LFA-1. IL-8, inducing the upregulation of MAC-1, did not elicit marker exocytosis in contact with EC. Our results suggest a role for PF-4 in the promotion of PMN-EC interaction that is virtually different from that exhibited by other CXC-chemokines such as IL-8.
Petersen
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F
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany. fpeters@fz-borstel.de
Bock
L
L
Flad
H D
HD
Brandt
E
E
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003029:Coagulants / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology*; D010978:Platelet Factor 4 / Q000494:pharmacology*
D003029:Coagulants; D016209:Interleukin-8; D010978:Platelet Factor 4