Induction and modulation of macrophage Ia antigen expression by platelet-activating factor.
Expression of major histocompatibility complex class II molecules, Ia, can be significantly augmented by interferon-gamma (IFN-gamma) in macrophages. In this study we demonstrate that platelet-activating factor (PAF) was also a potent inducer of Ia antigen expression on macrophages. PAF-induced Ia expression was both time- and dose-dependent. Maximal Ia expression was induced with 25 nM PAF after 3-h exposure to PAF. Ia expression in macrophages stimulated with PAF for 24 h was not significantly greater than unstimulated macrophages. Treatment of macrophages with IFN-gamma and PAF did not affect either the kinetics or concentration required for maximal Ia expression induced by either IFN-gamma or PAF. PAF-induced Ia expression was inhibited by the specific PAF receptor antagonists, WEB 2086, Ro 24-0238, and Ro 24-4637, indicating a receptor-mediated event. Like IFN-gamma-induced Ia expression, PAF activity was inhibited by prostaglandin E2 (PGE2). However, that expression was only inhibited after 24 h when macrophages were treated with the PGE2 synthesis inhibitors, flurbiprofen and indomethacin. These findings demonstrate that PAF, along with its role as a potent proinflammatory mediator, was also capable of inducing Ia expression on macrophages through the PAF receptor and that expression was altered by PGE2.
Erickson
K L
KL
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis 95616-8643, USA.
Howard
A D
AD
Hubbard
N E
NE
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D010972:Platelet Activating Factor; D007371:Interferon-gamma; D015232:Dinoprostone