Phospholipid arachidonic acid remodeling in macrophagesrole of plasmalogen species

Résumé

Macrophages provide large amounts of eicosanoids as they present high content of esterified arachidonic acid (AA). Free AA availability constitutes a rate limiting factor for eicosanoid synthesis during the innate immune response, and fatty acid mobilization is increased by bacterial lipopolysaccharide (LPS) priming before a subsequent stimulation. Moreover, AA is differentially distributed among membrane phospholipids, which is due to the action of coenzyme A-independent transacylase (CoA-IT), the enzyme that transfers the fatty acid primarily from diacyl phospholipid species to ether-containing species, mainly ethanolamine plasmalogens. In this work, the dependence of AA remodeling on plasmalogen content is analyzed in the murine macrophage cell line RAW264.7 and its plasmalogen-deficient variants RAW.12 and RAW.108, by using mass spectrometry-based lipidomic analyses. It is shown that LPS-primed zymosan-stimulated macrophages exhibit an increased consumption of ethanolamine plasmalogens, resulting from reduced phospholipid remodeling via CoA-IT-mediated reactions. AA remodeling between phospholipids preset similar kinetics both in presence and absence of plasmalogen species, thus indicating that cellular plasmalogen content does not influence the process. In addition, knockdown of cytosolic-group IVC phospholipase A2 (cPLA2γ) significantly reduced AA remodeling, which suggest an unrecognized role for cPLA2γ in supporting phospholipid composition through AA remodeling regulation.