Biologically Active Oxidized Phospholipids

A key component in the immediate response to inflammatory signals is the synthesis of PAF, a carefully regulated process. Oxidation of cellular and lipoprotein phosphatidylcholine through unregulated chemical reactions achieves the same end as these oxidative processes result in the formation of mimetics that are also potent activators of the inflammatory PAF receptor. Oxidation of LDL in vitro, where cellular regulation is moot, generates numerous lipid products that display several types of bioactivity. The best defined examples of bioactive neophospholipids are those that act through the PAF receptor. These PAF mimetics are found in vivo shortly after exposure to cigarette smoke, a powerful oxidative stress. Antioxidants or catabolism by the PAF acetylhydrolase counteract the formation of reactive and bioactive oxidized phospholipids, but these are not always sufficient. Oxidation of phosphatidylcholine generates other types of inflammatory mediators that clearly work in ways that do not require the PAF receptor. We anticipate, from the numerous types of products generated by phospholipid oxidation, that other activities and events caused by phospholipid oxidation will soon come to light.