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2014 ; 21
(10
): 1318-1329
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Maresin-like lipid mediators are produced by leukocytes and platelets and rescue
reparative function of diabetes-impaired macrophages
#MMPMID25200603
Hong S
; Lu Y
; Tian H
; Alapure BV
; Wang Q
; Bunnell BA
; Laborde JM
Chem Biol
2014[Oct]; 21
(10
): 1318-1329
PMID25200603
show ga
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-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acids, 14S,22-diHDHA
(maresin-L1), and 14R,22-diHDHA (maresin-L2) that are produced by leukocytes and
PLT and involved in wound healing. We show that 12-lipoxygenase-initiated
14S-hydroxylation or cytochrome P450 catalyzed 14R-hydroxylation and
P450-initiated ?(22)-hydroxylation are required for maresin-L biosynthesis.
Maresin-L treatment restores reparative functions of diabetic Mfs, suggesting
that maresin-Ls act as autocrine/paracrine factors responsible for, at least in
part, the reparative functions of leukocytes and PLT in wounds. Additionally,
maresin-L ameliorates Mf inflammatory activation and has the potential to
suppress the chronic inflammation in diabetic wounds caused by activation of Mfs.
These findings provide initial insights into maresin-L biosynthesis and mechanism
of action and potentially offer a therapeutic option for better treatment of
diabetic wounds.