Platelet-Activating Factor

Platelet-activating factor (PAF) is a phospholipid mediator with a very broad spectrum of potential biologic activities. Although early studies focused on its likely role in acute, IgE-mediated allergic reactions or as a naturally occurring antihypertensive agent, it has become apparent that its production and effects extend way beyond these arenas, from inflammation to parturition and development to actions in the nervous system. In actuality a family of related phospholipids with varying potency, or molecules with similar activity, may be produced by enzymatic or nonenzymatic means. As with all potent mediators there exist equally potent control mechanisms which include here rapid receptor desensitization and specific inactivating enzymes. PAF reacts with a seven transmembrane, heterotrimeric G protein-linked membrane receptor for which a knockout mouse has recently been created. A huge number of receptor antagonists have been synthesized and many are being explored in vitro, in animal models and in a variety of clinical trials. In addition, the complexity of the PAF story is increased by the observation that in the majority of cells that synthesize it, most of the PAF remains within the cell, leading to speculation that it plays an intracellular role, perhaps even on an intracellular receptor, in addition to its role as extracellular communication molecule.