title: Maresin-like lipid mediators are produced by leukocytes and platelets and rescue reparative function of diabetes-impaired macrophages.
abstract: 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.
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. Electronic address: shong@lsuhsc.edu.
authors.forename: Song
authors.initials: S
authors.lastname: Hong
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Haibin
authors.initials: H
authors.lastname: Tian
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Bhagwat V
authors.initials: BV
authors.lastname: Alapure
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
authors.affiliation: Department of Orthopedic Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70005, USA.
authors.forename: James Monroe
authors.initials: JM
authors.lastname: Laborde
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: C000596014:13,14-dihydroxydocosahexaenoic acid; C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; C553307:HGF protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D013929:Thromboxane B2; D017228:Hepatocyte Growth Factor; D003577:Cytochrome P-450 Enzyme System; D001092:Arachidonate 12-Lipoxygenase