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 s ecreted in high amounts by activated platelets. In previous studies, we fou nd that PF-4 specifically binds to human polymorphonuclear granulocytes (PM N), but requires tumor necrosis factor-alpha (TNF-alpha) as a costimulus fo r the induction of effector functions in suspended cells. In the present st udy, 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 gra nule contents in the presence of these cells. Interestingly, costimulation by TNF-alpha was not required, indicating that Pc could provide a correspon ding signal(s). As evident from antibody blocking experiments, PF-4-induced adhesion involved PMN-expressed L-selectin as well as leukocyte function-a ssociated 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-dependen t marker exocytosis from PMN, the costimulatory signal provided by Pc appea rs to be elicited through cell-cell contact via LFA-1. IL-8, inducing the u pregulation of MAC-1, did not elicit marker exocytosis in contact with Pc. 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 suc h as IL-8. (C) 1999 by The American Society of Hematology.