Polarization of Macrophages toward M2 Phenotype Is Favored by Reduction in iPLA2ß (Group VIA Phospholipase A2).
J Biol Chem
; 291(44): 23268-23281, 2016 10 28.
Article
em En
| MEDLINE
| ID: mdl-27650501
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 (iPLA2ß) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2ß in peritoneal macrophage immune function by comparing wild type (WT) and iPLA2ß-/- mouse macrophages. Compared with WT, iPLA2ß-/- macrophages exhibited reduced proinflammatory M1 markers when classically activated. In contrast, anti-inflammatory M2 markers were elevated under naïve conditions and induced to higher levels by alternative activation in iPLA2ß-/- 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 iPLA2ß-/- macrophages compared with WT. The effects of inhibitors of iPLA2ß, 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 iPLA2ß-/- macrophages, but none tested promoted M2 phenotype. These findings suggest that (a) lipids generated by iPLA2ß and subsequently oxidized by cyclooxygenase and 12-LO favor macrophage inflammatory M1 polarization, and (b) the absence of iPLA2ß promotes macrophage M2 polarization. Reducing macrophage iPLA2ß activity and thereby attenuating macrophage M1 polarization might cause a shift from an inflammatory to a recovery/repair milieu.
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MEDLINE
Assunto principal:
Polaridade Celular
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Fosfolipases A2 do Grupo VI
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Inflamação
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Macrófagos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article