Oxidatively fragmented phospholipids as inflammatory mediators: the dark side of polyunsaturated lipids

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.