Metabolism of platelet-activating factor by rat alveolar macrophages: lyso-PAF as an obligatory intermediate in the formation of alkylarachidonoyl glycerophosphocholine species.
1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC; platelet-activating factor; PAF) is actively taken up and metabolized by rat alveolar macrophages maintained in culture. The major metabolic products are lyso-PAF (alkyllyso-GPC) and alkylacyl-GPC. Lyso-PAF accumulates primarily in the media, whereas alkylacyl-GPC is predominantly associated with cellular lipids. The addition of unlabeled lyso-PAF to incubations initiated with [3H]PAF results in an increase in the amount of lyso-[3H]PAF product formed and a decrease in the final product, [3H]alkylacyl-GPC; however, the total amount of [3H]PAF metabolized remains unchanged. Unlabeled lyso-PAF thus enters the metabolic pool of the cell and competes with the deacetylated product of [3H]PAF, i.e., lyso-PAF, for acylation. High-performance liquid chromatography demonstrated that the reacylated product derived from lyso-PAF consisted primarily of the arachidonoyl-containing species that exists as the 16:0-20:4 molecular species. These results document that PAF is inactivated in rat alveolar macrophages via a deacetylation-reacylation reaction with lyso-PAF as an obligatory intermediate. The sequestering of arachidonic acid into the PAF precursor pool and the substantial amount of lyso-PAF secreted by macrophages into the extracellular fluid appear to be significant events in the inactivation process.
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats
C036761:1-alkyl-2-acyl-sn-glycero-3-phosphocholine; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor