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Oxidatively Fragmented Phospholipids as Inflammatory Mediators: The Dark Side of Polyunsaturated Lipids¹

Guy A. Zimmerman^*,,, Stephen M. Prescott^*, and Thomas M. McIntyre^*,,2

^* Department of Medicine Department of Biochemistry The Nora Eccles Harrison CVRTI the Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112

Phospholipids containing a polyunsaturated fatty acyl residue at the sn-2 position are common constituents of cellular membranes and lipoprotein particles. Just as free polyunsaturated fatty acids can be oxidized, derivatized, and fragmented, phospholipid acyl residues are also subject to similar oxidative attack. Oxidative modification and/or fragmentation of phosphatidylcholines generate potent inflammatory mediators that mimic the biologic action of platelet-activating factor (PAF). The oxidatively fragmented phospholipids with PAF-like activity act via the receptor for PAF and mimic most of its biologic actions. Thus, oxidation either through inappropriate inflammatory processes, endogenous oxygen metabolism or uptake of peroxidized lipids from the diet can all lead to inappropriate and unregulated generation of potent inflammatory mediators.

KEY WORDS: • platelet activation factor • low density lipoprotein • oxidation

¹ Presented as part of the symposium "Nutritional Modulation of Lipid-Mediated Signal Transduction Systems" given at Experimental Biology 94 meeting, Anaheim, CA, April 26, 1994. This symposium was sponsored by the American Institute of Nutrition and supported by a grant from the Mead Johnson Corporation. Guest editor for this symposium was Alfred H. Merrill, Jr., Emory University School of Medicine, Atlanta, GA.

² To whom correspondence should be addressed: CVRTI, Building 500, University of Utah, Salt Lake City, UT 84112.