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  • Title: Receptor-dependent metabolism of platelet-activating factor in murine macrophages.
    Author: Ohshima N, Ishii S, Izumi T, Shimizu T.
    Journal: J Biol Chem; 2002 Mar 22; 277(12):9722-7. PubMed ID: 11786559.
    Abstract:
    Degradation of platelet-activating factor (PAF) was examined by incubating PAF with macrophages from PAF receptor-deficient mice. The degradation rate was halved as compared with wild-type mice. The reduction of the rate was comparable with the presence of a PAF antagonist WEB 2086 in wild-type cells. PAF was internalized rapidly (t(12) approximately 1 min) into wild-type macrophages. The PAF internalization was inhibited by the treatment of 0.45 m sucrose but was not affected by phorbol 12-myristate 13-acetate, suggesting that PAF internalizes into macrophages with its receptor in a clathrin-dependent manner. Internalized PAF was degraded into lyso-PAF with a half-life of 20 min. Treatment of concanavalin A inhibited the conversion of PAF into lyso-PAF, suggesting that uptake of PAF enhances PAF degradation. Lyso-PAF was subsequently metabolized into 1-alkyl-2-acyl-phosphatidylcholine. In addition, release of PAF acetylhydrolase from macrophages was enhanced when wild-type macrophages were stimulated with PAF but not from macrophages of PAF receptor-deficient mice. Thus, the PAF stimulation of macrophages leads to its degradation through both intracellular and extracellular mechanisms.
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