Autacoid 14S,21R-dihydroxy-docosahexaenoic acid counteracts diabetic impairment of macrophage prohealing functions

15Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.

Abstract

Impaired macrophage functions imposed by diabetic complications and the suppressed formation of 14S,21R-dihydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA) in wounds contribute significantly to deficient wound healing in diabetics, but how are macrophage functions and 14S,21R-diHDHA formation associated? We studied 14S,21R-diHDHA generation from macrophages using liquid chromatography/mass spectrometry. The role in macrophage-mediated wound healing functions was determined using a murine splinted excisional wound healing model and in vitro assays. 14S,21R-diHDHA acts as a macrophage-generated autacoid, and its attenuated formation in macrophages of diabetic db/db mice was accompanied by impairment of macrophage prohealing functions. 14S,21R-diHDHA restored db/db macrophage-impaired prohealing functions by promoting wound re-epithelialization, formulation of granulation tissue, and vascularization. Additionally, 12/15-lipoxygenase-deficient macrophages, which are unable to produce 14S,21R-diHDHA, exhibited impaired prohealing functions, which also were restored by 14S,21R-diHDHA treatment. The molecular mechanism for 14S,21R-diHDHA-induced recovery of impaired prohealing functions of db/db macrophages involves enhancing their secretion of vascular endothelial growth factor and platelet-derived growth factor BB, decreasing hyperglycemia-induced generation of reactive oxygen species, and increasing IL-10 expression under inflammatory stimulation. Taken together, these results indicate that deficiency of 14S,21R-diHDHA formation by diabetic macrophages contributes to their impaired prohealing functions. Our findings provide mechanistic insights into wound healing in diabetics and suggest the possibility of using autologous macrophages/monocytes, treated with 14S,21R-diHDHA, or related compounds, to promote diabetes-impaired wound healing. © 2011 American Society for Investigative Pathology.

Cite

CITATION STYLE

APA

Tian, H., Lu, Y., Shah, S. P., & Hong, S. (2011). Autacoid 14S,21R-dihydroxy-docosahexaenoic acid counteracts diabetic impairment of macrophage prohealing functions. American Journal of Pathology, 179(4), 1780–1791. https://doi.org/10.1016/j.ajpath.2011.06.026

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free