biostudies-literatureNelson AJBLRD VANICHD NIH HHSthe King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (A.A.); Veterans AdministrationNIDDK NIH HHSIacocca Family FoundationNIAID NIH HHSNHLBI NIH HHSNational Institutes of HealthNIGMS NIH HHS143-158https://www.ebi.ac.uk/biostudies/studies/S-EPMC6997598biostudies-literatureUnknown61(2)Phospholipases A₂ (PLA₂s) catalyze hydrolysis of the <i>sn</i>-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca²⁺-independent phospholipase A₂ (PLA₂)β (iPLA₂β). Here, we assessed the link between iPLA₂β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (<i>iPLA₂β-/-</i>) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed Journal of lipid researchMacrophage polarization is linked to Ca²⁺-independent phospholipase A₂β-derived lipids and cross-cell signaling in mice.PMC6997598R01 DK069455R01 DK69455R01 DK110292RR031535R01 HL125353P30 DK079626T32 GM008111R01 AI139072I01 BX001792U01 HD087198IK6 BX004603Nelson AJBarbour SERamanadham SChalfant CELei XCardona CLStephenson DJTusing YGPark MAWhite TDAlmutairi AfalseMacrophage polarization is linked to Ca²⁺-independent phospholipase A₂β-derived lipids and cross-cell signaling in mice.Phospholipases A₂ (PLA₂s) catalyze hydrolysis of the <i>sn</i>-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca²⁺-independent phospholipase A₂ (PLA₂)β (iPLA₂β). Here, we assessed the link between iPLA₂β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (<i>iPLA₂β-/-</i>) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed 2020-01-01T00:00:00Z2020 Feb2025-04-22T09:35:05.727Z2021-02-21T04:28:20ZS-EPMC69975983181887710.1194/jlr.RA11900028110.1194/jlr.ra119000281