Novel Neutrophil Agonists: Oxidatively-Fragmented Phosphatidylcholines
Platelet-activating factor (PAF) is a phospholipid autocoid that plays a role in both physiologic and pathologic events. Its diverse biologic activities include activation of platelets, neutrophils, macrophages, and other cell types not directly involved in the inflammatory process1. When exogenously administered, PAF produces the symptoms of anaphylactic shock. It is obviously important that the synthetic and degradative enzymes controlling its production and metabolism be tightly regulated. PAF acts via receptors2 present on the cell membrane of target cells; the structural requirements for high affinity binding and activation of PAF receptors have been well characterized3. The ether linkage at the sn-1 position, short chain acetyl residue at the sn-2 position, and phosphocholine group at the sn-3 position of PAF all play an important role in this high affinity recognition. Phospholipids other than PAF are capable of binding to and activating the PAF receptor. For example the 1-O-alkyl-2-propionoyl homolog is twice as potent as PAF. Other homologs are active but less potent. The sn-2 butyroyl homolog is 30-100-fold less potent than PAF3, while the succinoyl and glutaroyl homologs are several hundred-fold less potent3. The presence of an ester linkage at the sn-1 position instead of an ether linkage results in a several hundred-fold loss in potency3.
KeywordsRhizopus Arrhizus Butyl Hydroperoxide Oxidative Fragmentation Bond Rearrangement Phosphocholine Group
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