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

Article

关键词: PHOSPHATIDIC-ACID;    MACROPHAGE POLARIZATION;    TUMOR-GROWTH;    RECEPTOR;    CANCER;    EXPRESSION;    PLD2;    IDENTIFICATION;    ADHESION;    ROLES;   

DOI  :  10.1096/fj.201903025RR

来源: SCIE

【 摘 要 】

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 increasing PLD2 expression and activity; and (b) RvD5 enhances PLD2-S6Kinase signaling required for membrane expansion and efferocytosis. In anin vivomodel 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 as the isoform in RvD5-mediated resolution processes. These results demonstrate that RvD5-PLD2 are attractive targets for therapeutic interventions in vascular inflammation such as ischemia-reperfusion injury and cardiovascular diseases.

【 授权许可】

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