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

Lysophosphatidylcholine is an abundant component of plasma and oxidized LDL that displays several biological activities, some of which may occur throu gh the platelet-activating factor (PAE) receptor. We find that commercial l ysophosphatidylcholine, its alkyl homolog (lyso-PAF), and PAF all induce in flammation in a murine model of pleurisy. Hydrolysis of PAF to lyso-PAF by recombinant PAF acetylhydrolase abolished this eosinophilic infiltration, i mplying that lyso-PAF should not have displayed inflammatory activity. Sapo nification of lyso-PAF or PAF acetylhydrolase treatment of lyso-PAF or lyso phosphatidylcholine abolished activity; neither lysolipid should contain su sceptible sn-2 residues, suggesting contaminants account for the bioactivit y. Lyso-PAF and to a lesser extent lysophosphatidylcholine stimulated Ca2accumulation in 293 cells stably transfected with the human PAF receptor, a nd this was inhibited by specific PAF receptor antagonists. Again, treatmen t of lyso-PAF or lysophosphatidylcholine with recombinant PAF acetylhydrola se, a nonselective phospholipase A(2), or saponification of lyso-PAF destro yed the PAF-like activity, a result incompatible,with lyso-PAF or lysophosp hatidylcholine being the actual agonist. We conclude that neither lyso-PAF nor lysophosphatidylcholine is a PAF receptor agonist, nor are they inflamm atory by themselves. We suggest that PAF or a PAF-like mimetic accounts for inflammatory effects of lysophosphatidylcholine and lyso-PAF.