Department of Medicine, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Biomolecules. 2020 Dec 29;11(1):25. doi: 10.3390/biom11010025.
Macrophages activated by Interleukin (IL)-4 (M2) or LPS+ Interferon (IFN)γ (M1) perform specific functions respectively in type 2 inflammation and killing of pathogens. Group V phospholipase A (Pla2g5) is required for the development and functions of IL-4-activated macrophages and phagocytosis of pathogens. Pla2g5-generated bioactive lipids, including lysophospholipids (LysoPLs), fatty acids (FAs), and eicosanoids, have a role in many diseases. However, little is known about their production by differentially activated macrophages. We performed an unbiased mass-spectrometry analysis of phospholipids (PLs), LysoPLs, FAs, and eicosanoids produced by Wild Type (WT) and -null IL-4-activated bone marrow-derived macrophages (IL-4)BM-Macs (M2) and (LPS+IFNγ)BM-Macs (M1). Phosphatidylcholine (PC) was preferentially metabolized in (LPS+IFNγ)BM-Macs and Phosphatidylethanolamine (PE) in (IL-4)BM-Macs, with Pla2g5 contributing mostly to metabolization of selected PE molecules. While Pla2g5 produced palmitic acid (PA) in (LPS+IFNγ)BM-Macs, the absence of Pla2g5 increased myristic acid (MA) in (IL-4)BM-Macs. Among eicosanoids, Prostaglandin E (PGE) and prostaglandin D (PGD) were significantly reduced in (IL-4)BM-Macs and (LPS+IFNγ)BM-Macs lacking Pla2g5. Instead, the IL-4-induced increase in 20-carboxy arachidonic acid (20CooH AA) was dependent on Pla2g5, as was the production of 12-hydroxy-heptadecatrienoic acid (12-HHTrE) in (LPS+IFNγ)BM-Macs. Thus, Pla2g5 contributes to PE metabolization, PGE and PGD production independently of the type of activation, while in (IL-4)BM-Macs, Pla2g5 regulates selective lipid pathways and likely novel functions.
白细胞介素 (IL)-4 激活的巨噬细胞（M2）或 LPS+干扰素 (IFN)γ 激活的巨噬细胞（M1）分别在 2 型炎症和病原体杀伤中发挥特定功能。组 V 磷脂酶 A（Pla2g5）是 IL-4 激活的巨噬细胞的发育和功能以及病原体吞噬所必需的。Pla2g5 产生的生物活性脂质，包括溶血磷脂（LysoPL）、脂肪酸（FA）和类二十烷酸，在许多疾病中发挥作用。然而，对于不同激活的巨噬细胞产生的这些脂质知之甚少。我们对野生型 (WT) 和 -null IL-4 激活的骨髓来源巨噬细胞（IL-4）BM-Macs（M2）和（LPS+IFNγ）BM-Macs（M1）产生的磷脂（PL）、溶血磷脂（LysoPL）、FA 和类二十烷酸进行了无偏质谱分析。在（LPS+IFNγ）BM-Macs 中，磷脂酰胆碱（PC）优先代谢，在（IL-4）BM-Macs 中，磷脂酰乙醇胺（PE）优先代谢，而 Pla2g5 主要参与选择的 PE 分子的代谢。虽然 Pla2g5 在（LPS+IFNγ）BM-Macs 中产生棕榈酸（PA），但 Pla2g5 的缺失会增加（IL-4）BM-Macs 中的肉豆蔻酸（MA）。在类二十烷酸中，前列腺素 E（PGE）和前列腺素 D（PGD）在缺乏 Pla2g5 的（IL-4）BM-Macs 和（LPS+IFNγ）BM-Macs 中显著减少。相反，IL-4 诱导的 20-羧基花生四烯酸（20CooH AA）的增加依赖于 Pla2g5，而在（LPS+IFNγ）BM-Macs 中，12-羟基-十七碳三烯酸（12-HHTrE）的产生也依赖于 Pla2g5。因此，Pla2g5 有助于 PE 代谢，独立于激活类型产生 PGE 和 PGD，而在（IL-4）BM-Macs 中，Pla2g5 调节选择性脂质途径和可能的新功能。
