Stimulation of monocytes and platelets by short-chain phosphatidylcholines with and without terminal carboxyl group.
Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.
Department of Anesthesiology and Intensive Care Medicine, University Hospital Charité, Humboldt-University, Schumannstr. 20-21, 10117 Berlin, Germany.
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Kern
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Volk
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Knauer-Schiefer
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Mieth
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Rüstow
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Kox
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Schlame
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship
D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D012701:Serotonin; D002118:Calcium