D‐series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution

Abstract

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 proresolving 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 increasing PLD2 expression and activity; and (b) RvD5 enhances PLD2-S6Kinase signaling required for membrane expansion and efferocytosis. In an in vivo model of second organ reflow injury, we found that RvD5 did not reduce lung neutrophil myeloperoxidase levels in PLD2-/mice compared to WT and PLD1-/mice, confirming a novel role of PLD2 2 | GANESAN Et Al.

Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages

“…To investigate whether RvD1 elicits an anti-inflammatory and proresolution effect in the presented co-culture system comparable to its effect observed in mouse adipose tissue in vivo [18,19,21,22], we performed the co-culture experiments in the presence of 10, 100, and 500 nM RvD1, covering the concentration range previously shown to effect human cells expressing the RvD1 receptor ALX/FPR2 and/or GPR32 [32,38,39]. Therefore, 6 day old macrophages were incubated with RvD1 for two days and then transferred to 28 day old adipocytes.…”

Evaluation of the effects of Loxosceles intermedia’s venom in zebrafish

“…Despite no observed alterations upon LIV injection, we aimed to analyse if SPMs could modulate regeneration. RvD5 was selected given it has been shown to inhibit PLD activity, shifting macrophage phenotype to M2 [30] . Although MaR1 is known to induce tissue regeneration [31] , this activity had not been investigated for MaR2 yet.…”

Updated Views on Neutrophil Responses in Ischemia–Reperfusion Injury

“…30,98 These findings suggest that IRI-mediated injury is associated with rapid recruitment of neutrophils that undergo extravasation and activation within ischemic tissues, followed by a phase of inflammation resolution mediated by specialized proresolving lipid mediators, such as resolvins, which can be released from a variety of cells including macrophages and neutrophils. 99,100 In canine heart and rat liver IRI models, NADPH oxidase-mediated ROS production by neutrophils has been identified as an important effector arm of tissue damage. 101,102 Neutrophil elastase release by activated neutrophils can also mediate tissue damage in animal models of lung and hepatic IRI.…”

“…30,98 These findings suggest that IRI-mediated injury is associated with rapid recruitment of neutrophils that undergo extravasation and activation within ischemic tissues, followed by a phase of inflammation resolution mediated by specialized proresolving lipid mediators, such as resolvins, which can be released from a variety of cells including macrophages and neutrophils. 99,100…”