Maresin-like Lipid Mediators Are Produced by Leukocytes and Platelets and Rescue Reparative Function of Diabetes-Impaired Macrophages

摘要: Summary Nonhealing diabetic wounds are associated with impaired macrophage (Mf) function. Leukocytes and platelets (PLT) play crucial roles in wound healing by poorly understood mechanisms. Here we report the identification and characterization of the maresin-like(L) mediators 14,22-dihydroxy-docosa-4 Z ,7 ,10 ,12 E ,16 ,19 -hexaenoic acids, 14 S ,22-diHDHA (maresin-L1), R (maresin-L2) that produced by leukocytes and PLT involved healing. We show 12-lipoxygenase-initiated -hydroxylation or cytochrome P450 catalyzed P450-initiated ω(22)-hydroxylation required for maresin-L biosynthesis. Maresin-L treatment restores reparative functions of Mfs, suggesting maresin-Ls act as autocrine/paracrine factors responsible for, at least part, the PLT wounds. Additionally, maresin-L ameliorates Mf inflammatory activation has potential to suppress chronic inflammation caused Mfs. These findings provide initial insights into biosynthesis mechanism action potentially offer a therapeutic option for better