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 docosa-hexaenoic 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.
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