P-selectin regulates platelet-activating factor synthesis and phagocytosis by monocytes.
Adhesion molecules on endothelial cells or platelets may regulate localization and activation of leukocytes at sites of tissue injury, infection, or thrombosis. In these studies, we found that human peripheral blood monocytes adhered specifically to immobilized P-selectin (CD62P), Chinese hamster ovary cells transfected with a cDNA for P-selectin, or endothelial cells stimulated to express P-selectin on the cell surface. P-selectin did not directly stimulate synthesis of the lipid autoacoid platelet-activating factor (PAF); however, incubation on immobilized P-selectin primed monocytes for increased synthesis of PAF in response to opsonized zymosan particles. P-selectin did not stimulate increased surface expression of integrin CD11b/CD18 and did not enhance binding of iC3b-coated erythrocytes, a CD11b/CD18-mediated functional response. P-selectin increased PAF production by monocytes incubated with unopsonized zymosan particles that stimulate this response by interaction with the beta-glucan receptor. Further, phagocytosis of unopsonized zymosan particles, another response triggered by the beta-glucan receptor, was increased following the adherence of monocytes to P-selectin. These data suggested that P-selectin primed monocytes for increased PAF synthesis through regulation of the beta-glucan receptor or regulation of signal transduction mechanisms that are linked to the receptor. P-selectin expressed on endothelial cells or platelets may serve both to localize monocytes at sites of vascular inflammation or thrombosis and to prime the cells for subsequent responses that augment inflammation.
Elstad
M R
MR
Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA.
La Pine
T R
TR
Cowley
F S
FS
McEver
R P
RP
McIntyre
T M
TM
Prescott
S M
SM
Zimmerman
G A
GA
D000818:Animals; D018845:CD11 Antigens / Q000032:analysis / Q000502:physiology; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D005609:Free Radicals; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D019007:P-Selectin; D010587:Phagocytosis / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D018845:CD11 Antigens; D018821:CD18 Antigens; D005609:Free Radicals; D019007:P-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D013481:Superoxides