Composition of Alkyl Ether-Linked Phospholipids in Mammalian Tissues

Abstract

In 1979, the structure of a lipid chemical mediator of hypersensitivity, platelet-activating factor (PAF) (Benveniste et al., 1972), was proposed to be that of an alkyl ether-containing phospholipid, l-O-alkyl-2-acetyl-sn-glycero-3-phosphocho-line (Benveniste et al., 1979; Demopoulos et al., 1979). Final elucidation of the structure of PAF from IgE-sensitized rabbit basophils was performed in 1980 (Hanahan et al., 1980). The presence of an alkyl ether moiety at the sn-1 position of the glycerol backbone was found to be critically important. At the same time, this unique ether phospholipid was reported to cause dramatic hypotension in a one-kidney, one-clip hypertensive rat (Blank et al., 1979). Thus, the first description of the PAF structure was reported by three independent groups. Moreover, recent precise studies by many investigators revealed that PAF exhibits, in fact, a variety of potent biological activities other than the platelet-activating and hypotensive activities (Benveniste and Arnoux, 1983; Benveniste and Vargaftig, 1983; Lee and Snyder, 1984). For instance, a low concentration of PAF activates or causes the aggregation of leukocytes such as neutrophils, macrophages, and monocytes. PAF was also shown to increase vascular permeability and to cause bronchoconstriction, smooth muscle contraction, constriction of the coronary artery in isolated guinea pig heart, and glycogenosis in perfused rat liver. Very recently, PAF was shown to induce the secretion of amylase in guinea pig pancreas (Söling et al., 1984). The above observations strongly suggest that PAF acts as an autacoid or hormonelike substance in vivo, particularly in inflammatory reactions. The target tissues or cells of PAF seem to be widely spread in the mammalian body.