Polarization of macrophages toward M2 phenotype is favored by reduction in iPLA2β Group VIA phospholipase a2

Jason W. Ashley, William D. Hancock, Alexander J. Nelson, Robert N. Bone, Hubert M. Tse, Mary Wohltmann, John Turk, Sasanka Ramanadham

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Macrophages are important in innate and adaptive immunity. Macrophage participation in inflammation or tissue repair is directed by various extracellular signals and mediated by multiple intracellular pathways. Activation of group VIA phospholipase A2 (iPLA2β) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2β in peritoneal macrophage immune function by comparing wild type (WT) and iPLA2β-/- mouse macrophages. Compared with WT, iPLA2β -/- macrophages exhibited reduced proinflammatory M1 markers when classically activated. In contrast, antiinflammatory M2 markers were elevated under naïve conditions and induced to higher levels by alternative activation in iPLA2β-/- macrophages compared with WT. Induction of eicosanoid (12-lipoxygenase (12-LO) and cyclooxygenase 2 (COX2))- and reactive oxygen species (NADPH oxidase 4 (NOX4))-generating enzymes by classical activation pathways was also blunted in iPLA2β-/- macrophages compared with WT. The effects of inhibitors of iPLA2β, COX2, or 12-LO to reduce M1 polarization were greater than those to enhance M2 polarization. Certain lipids (lysophosphatidylcholine, lysophosphatidic acid, and prostaglandin E2 ) recapitulated M1 phenotype in iPLA2 β-/- macrophages, but none tested promoted M2 phenotype. These findings suggest that (a) lipids generated by iPLA2β and subsequently oxidized by cyclooxygenase and 12-LO favor macrophage inflammatory M1 polarization, and (b) the absence of iPLA2β promotes macrophage M2 polarization. Reducing macrophage iPLA2β activity and thereby attenuating macrophage M1 polarization might cause a shift from an inflammatory to a recovery/repair milieu.

Original languageEnglish
Pages (from-to)23268-23281
Number of pages14
JournalJournal of Biological Chemistry
Volume291
Issue number44
DOIs
StatePublished - Oct 28 2016

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    Ashley, J. W., Hancock, W. D., Nelson, A. J., Bone, R. N., Tse, H. M., Wohltmann, M., Turk, J., & Ramanadham, S. (2016). Polarization of macrophages toward M2 phenotype is favored by reduction in iPLA2β Group VIA phospholipase a2. Journal of Biological Chemistry, 291(44), 23268-23281. https://doi.org/10.1074/jbc.M116.754945