TY - JOUR
T1 - Maresin-like lipid mediators are produced by leukocytes and platelets and rescue reparative function of diabetes-impaired macrophages
AU - Hong, Song
AU - Lu, Yan
AU - Tian, Haibin
AU - Alapure, Bhagwat V.
AU - Wang, Quansheng
AU - Bunnell, Bruce A.
AU - Laborde, James Monroe
N1 - Funding Information:
This research was funded by NIH Grant R01-DK087800 (to S.H.) and Research to Prevent Blindness, New York. We thank Drs. Nicolas G. Bazan and Haydee E.P. Bazan for providing the L12-LO −/− mice, Mr. Ryan Labadens and Yue-Liang Brewerton for editing, and Shirley N. Hong for graphic assistance.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/10/23
Y1 - 2014/10/23
N2 - 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-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 ω(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.
AB - 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-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 ω(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.
UR - http://www.scopus.com/inward/record.url?scp=84908334568&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2014.06.010
DO - 10.1016/j.chembiol.2014.06.010
M3 - Article
C2 - 25200603
AN - SCOPUS:84908334568
SN - 1074-5521
VL - 21
SP - 1318
EP - 1329
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 10
ER -