RT Journal Article SR Electronic T1 PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaar8320 DO 10.1126/sciadv.aar8320 VO 4 IS 9 A1 Loynes, Catherine A. A1 Lee, Jou A. A1 Robertson, Anne L. A1 Steel, Michael JG. A1 Ellett, Felix A1 Feng, Yi A1 Levy, Bruce D. A1 Whyte, Moira K.B. A1 Renshaw, Stephen A. YR 2018 UL http://advances.sciencemag.org/content/4/9/eaar8320.abstract AB Neutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site—either by apoptosis and efferocytosis or by reverse migration away from the wound—for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve, due to loss of macrophage-dependent handling of eicosanoid prostaglandin E2 (PGE2) that drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous PGE synthase gene reveals PGE2 as essential for neutrophil inflammation resolution. Furthermore, PGE2 is able to signal through EP4 receptors during injury, causing an increase in Alox12 production and switching toward anti-inflammatory eicosanoid signaling. Our data confirm regulation of neutrophil migration by PGE2 and LXA4 (lipoxin A4) in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease.