Platelet-activating factor: a phospholipid autacoid with diverse actions

Platelet-activating factor (PAF, 1-0-alkyl-2-acetyl-snglycero-3-phosphocholine) is a potent biological mediator that exerts its effects in a variety of cells and tissues (1-3). This phospholipid mediator was discovered during concurrent investigations of a factor derived from the blood of rabbits undergoing anaphylaxis that activated platelets, and an endogenous polar lipid from kidney that lowered blood pressure. When the common structures were elucidate,d, a new field of research had emerged (reviewed in 1, 2 by the leaders of the two groups that determined the structure). The trivial name, .PAF, is a misnomer as it describes only one of the compound’s many effects. This name, however, has been retained due to the lack of a suitable alternative. Other acronyms that include structural information, e.g., AGEPC (alkyl glycerol ether phosphoryl choline) and PAFacether, have been proposed as substitutes but have not found wide acceptance. PAF is unique in its role as a phospholipid that functions as an intercellular mediator, and it may also function as an intracellular messenger. It acts through a specific receptor, for which a cDNA has been cloned and expressed in mammalian cells. PAF is synthesized by one of two pathways, the first involving the remodeling of cell membrane phospholipids by the hydrolysis of an arachidonate from the sn-2 position and its replacement with an acetate. The second route entails its de novo synthesis from 1-0-alkyl-sn-glycero-3-phosphate hrough the incorporation of an acetate, removal of the phosphate, and its replacement with phosphocholine. PAF is degraded by the removal of the acetate and re-acylation with a fatty acid. The structural elements of PAF are each important for optimal biological activity. Modification of the etherlinkage of the fatty alkyl group at the sn-1 position of the glycerol backbone, the short chain acyl residue (acetate) sn-glycero-3-phosphocholine as PAF, without regard for the length or the degree of unsaturation of the alkyl chain at the sn-1 position, and to refer to structurally related compounds as PAF analogs. These PAF analogs may have substantial bioactivity and participate in signaling in vivo. Some of the most recent findings were presented at the Fourth International Congress on PAF and Related Lipid Mediators in September, 1992 and will be published as brief reports in a special issue of the Jouml OfLipid Mediaton.