Platelet Factor 4-Induced Neutrophil-Endothelial Cell Interaction: Involvement of Mechanisms and Functional Consequences Different From Those Elicited by Interleukin-8

Abstract

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- (TNF-) 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- 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.