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‐γ (IFN‐γ) 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‐γ and PAF did not affect either the kinetics or concentration required for maximal Ia expression induced by either IFN‐γ 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‐γ‐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. J. Leukoc. Biol. 62: 845–851; 1997.