Abstract
The platelet-activating factor (PAF) is an endogenous lipid mediator derived from membrane phospholipids. PAF was discovered in 1972 as a fluid-phase mediator released from IgE-stimulated basophils that induce the aggregation of rabbit platelets. Biological activity relevant to inflammatory reaction has also been demonstrated, subsequent to identification of the structure of PAF as 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine in 1979. The activity includes activation of leukocytes, increased vascular permeability and contraction of smooth muscle. In the search for antagonists from synthetic analogues of PAF and natural products, a number of antagonists that act on cell surface receptors have been found. A c-DNA for a PAF receptor was cloned first by Shimizu et al. in 1991. PAF is inactivated by the enzyme, PAF-acetylhydrolase, which removes the sn-2 acetyl group of PAF. Discovery of the deficiency of this enzyme, reported by Miwa et al. in 1988, prompted attention to its relationship with diseases such as bronchial asthma. The molecular cloning of intracellular- and plasma-type PAF-acetylhydrolases was achieved in 1994 and 1995, respectively. The isolation of these genes made possible elucidation of the role of PAF in inflammatory reactions on a molecular basis. Recent progress in the study of this factor by a genetical approach is discussed in detail.
