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Biosynthetic labelling of platelet activating factor from radioactive acetate by stimulated platelets

Abstract

Platelet activating factor (PAF-acether) is a chemical mediator released by basophils in in vitro and in vivo conditions of immunological challenge1–5. PAF-acether induces aggregation and secretion of platelets from different species3,6,7 and could thus be implicated in various immunological forms of tissue injury8,9. Other sources have been described for this mediator, including macrophages10 and platelets11. As the amounts of PAF-acether released in the latter case are sufficient to support the platelet aggregation11 and as platelet aggregation by PAF-acether does not require ADP secretion or thromboxane biosynthesis12, PAF-acether was proposed as the mediator of the putative third pathway of platelet aggregation11. Structural analysis of PAF-acether by lipases indicated that it could be a glycerophospholipid devoid of an ester linkage at the 1-position and bearing a fatty acid esterified at the 2-position13. This has provided the first evidence for a phospholipid displaying the properties of a powerful chemical mediator. Based on several lines of evidence, l-O-alkyl-2-acetyl-sn-glyceryl-3-phos-phorylcholine (l-alkyl-2-acetyl-GPC) was recently proposed as the chemical structure of the mediator, hence the term PAF-acether14,15. As PAF-acether synthesis occurs rather early in activated platelets, one of the most efficient pathways of PAF-acether formation could involve a rapid acetylation of the corresponding lysoderivative (1-alkyl-GPC). We now present evidence that platelets activated by ionophore A23187 are able to incorporate acetate into a mixture of l-alkyl-2-acetyl-GPC and l-acyl-2-acetyl-GPC; the former supports the biological activity of PAF-acether.

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Chap, H., Mauco, G., Simon, M. et al. Biosynthetic labelling of platelet activating factor from radioactive acetate by stimulated platelets. Nature 289, 312–314 (1981). https://doi.org/10.1038/289312a0

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