Eosinophils promote resolution of acute peritonitis by producing proresolving mediators in mice.
Acute inflammation in healthy individuals is self-limiting and has an active termination program. The mechanisms by which acute inflammation is resolved are of interest. In murine zymosan-induced peritonitis, we found that eosinophils are recruited to the inflamed loci during the resolution phase of acute inflammation. In vivo depletion of eosinophils caused a resolution deficit, namely impaired lymphatic drainage with reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph node, and sustained numbers of polymorphonuclear leukocytes in inflamed tissues. Liquid chromatography-tandem mass spectrometry-based lipidomics of the resolving exudates revealed that locally activated eosinophils in the resolution phase produced proresolving mediators, including protectin D1 (PD1) from docosahexaenoic acid. The resolution deficit caused by eosinophil depletion was rescued by eosinophil restoration or the administration of PD1. Eosinophils deficient in 12/15-lipoxygenase could not rescue the resolution phenotype. The present results indicate that mouse eosinophils and eosinophil-derived lipid mediators, including PD1, have a role in promoting the resolution of acute inflammation, expanding the roles of eosinophils in host defense and resolution.
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tomohiro
T
Yamada
Yukako
Y
Tani
Hiroki
H
Nakanishi
Ryo
R
Taguchi
Makoto
M
Arita
Hiroyuki
H
Arai
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004804:Eosinophils / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors; D015054:Zymosan / Q000633:toxicity
C475064:12-15-lipoxygenase; C487679:protectin D1; D004281:Docosahexaenoic Acids; D015054:Zymosan; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase