Bioactive phospholipid oxidation products

Oxidation of phospholipids results in chain-shortened fragments and oxygena ted derivatives of polyunsaturated sn-2 fatty acyl residues, generating a m yriad of phospholipid products. Certain oxidation products of phosphatidylc holine bind to and activate the human receptor fur PAF, and these PAF-like Lipids are potent, selective inflammatory mediators. Formation of PAF-like lipids is nonenzymatic and so their accumulation is unregulated. PAF-like l ipids are produced in vivo in response to oxidative stresses and are respon sible for attendant acute inflammatory responses, PAF-like lipids almost ex clusively contain an ether-linked alkyl residue at the sn-l position of the phosphatidylcholine backbone and molecular identification of these is faci litated by phospholipase A(1) treatment to remove the bulk of the inactive phospholipids. The identity of biologically active species generated by oxi dative fragmentation and oxidation can be elucidated by understanding relev ant reactions lending to the formation of PAF-like lipids, and then their s tructure can be established by tandem mass spectrometry and chemical synthe sis. (C) 2000 Elsevier Science Inc.