biostudies-literatureGanesan RAmerican Heart AssociationNHLBI NIH HHSNational Institutes of HealthNIGMS NIH HHS15888-15906https://www.ebi.ac.uk/biostudies/studies/S-EPMC7686130biostudies-literatureUnknown34(12)A successful acute inflammatory response results in the elimination of infectious agents by neutrophils and monocytes, followed by resolution and repair through tissue-resident and recruited macrophages. Resolvins (D-series and E-series) are pro-resolving lipid mediators involved in resolution and tissue repair, whose intracellular signaling remains of interest. Here, we report that D-series resolvins (RvD1- RvD5) activate phospholipase D (PLD), a ubiquitously expressed membrane lipase enzyme activity in modulating phagocyte functions. The mechanism for PLD-mediated actions of Resolvin-D5 (RvD5) in polarizing macrophages (M1-like toward M2-like) was found to be two-pronged: (a) RvD5 inhibits post-transcriptional modifications, by miRs and 3'exonucleases that process PLD2 mRNA, thus increasFASEB journal : official publication of the Federation of American Societies for Experimental BiologyD-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.PMC7686130R01 HL056653P01 GM09546713GRNT17230097R29 HL056653P01GM095467HL056653‐14Henkels KMGanesan RCheemarla NRGomez-Cambronero JSerhan CNDe La Rosa XLibreros SShah KfalseD-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.A successful acute inflammatory response results in the elimination of infectious agents by neutrophils and monocytes, followed by resolution and repair through tissue-resident and recruited macrophages. Resolvins (D-series and E-series) are pro-resolving lipid mediators involved in resolution and tissue repair, whose intracellular signaling remains of interest. Here, we report that D-series resolvins (RvD1- RvD5) activate phospholipase D (PLD), a ubiquitously expressed membrane lipase enzyme activity in modulating phagocyte functions. The mechanism for PLD-mediated actions of Resolvin-D5 (RvD5) in polarizing macrophages (M1-like toward M2-like) was found to be two-pronged: (a) RvD5 inhibits post-transcriptional modifications, by miRs and 3'exonucleases that process PLD2 mRNA, thus increas2020-01-01T00:00:00Z2020 Dec2025-04-21T21:42:42.429Z2022-02-11T13:14:40.918ZS-EPMC76861303304735910.1096/fj.201903025RR10.1096/fj.201903025rr