Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases

Platelet-activating factor (PAF) mediates a variety of physiologic and pathologic events by activating platelets, neutrophils, monocytes, macrophages, and smooth muscle cells. A strongly oxidizing environment induces fragmentation of the polyunsaturated fatty acids of membrane phospholipids, and the resulting oxidized phospholipids are structurally similar to PAF and mimic its biologic actions. The effects of PAF and oxidized phospholipids are abolished by hydrolysis of the sn-2 residue, a reaction catalyzed by PAF acetylhydrolase. Plasma and intracellular forms of PAF acetylhydrolase have been purified and characterized. The plasma form binds with high affinity to lipoproteins in plasma. Furthermore, changes in the activity of this enzyme are associated with various human diseases and animal models of human pathology, suggesting that it may play important roles in their pathogenesis. Studies that have defined the properties of this enzyme and its roles in physiologic and pathologic processes are reviewed. Such studies have provided insight into the functions of PAF and oxidized phospholipids as well as into the etiology of allergic, inflammatory, and atherosclerotic diseases.