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.