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Journal of Lipid Research, Vol. 42, 1430-1437, September 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids

Correspondence to: Thomas M. McIntyre, at 4130 EIHG, 2030 East 15 North, University of Utah, Salt Lake City, UT 84112., tom.mcintyre{at}hmbg.utah.edu (E-mail)

Lysophosphatidylcholine is an abundant component of plasma and oxidized LDL that displays several biological activities, some of which may occur through the platelet-activating factor (PAF) receptor. We find that commercial lysophosphatidylcholine, its alkyl homolog (lyso-PAF), and PAF all induce inflammation in a murine model of pleurisy. Hydrolysis of PAF to lyso-PAF by recombinant PAF acetylhydrolase abolished this eosinophilic infiltration, implying that lyso-PAF should not have displayed inflammatory activity. Saponification of lyso-PAF or PAF acetylhydrolase treatment of lyso-PAF or lysophosphatidylcholine abolished activity; neither lysolipid should contain susceptible sn-2 residues, suggesting contaminants account for the bioactivity. Lyso-PAF and to a lesser extent lysophosphatidylcholine stimulated Ca²⁺ accumulation in 293 cells stably transfected with the human PAF receptor, and this was inhibited by specific PAF receptor antagonists. Again, treatment of lyso-PAF or lysophosphatidylcholine with recombinant PAF acetylhydrolase, a nonselective phospholipase A₂, or saponification of lyso-PAF destroyed the PAF-like activity, a result incompatible with lyso-PAF or lysophosphatidylcholine being the actual agonist.

We conclude that neither lyso-PAF nor lysophosphatidylcholine is a PAF receptor agonist, nor are they inflammatory by themselves. We suggest that PAF or a PAF-like mimetic accounts for inflammatory effects of lysophosphatidylcholine and lyso-PAF. — Marathe, G. K., A. R. Silva, H. C. de Castro Faria Neto, L. W. Tjoelker, S. M. Prescott, G. A. Zimmerman, and T. M. McIntyre. Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids. J. Lipid Res. 2001. 42: 1430;–1437.

Supplementary key words: LPC, inflammation, neutrophil, PAF receptor

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