PGE Production at Sites of Tissue Injury Promotes an Anti-inflammatory Neutrophil Phenotype and Determines the Outcome of Inflammation Resolution in Vivo

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2018 Sep 8

PMID 30191175

Citations 100

Authors

Catherine A Loynes

Jou A Lee

Anne L Robertson

Michael Jg Steel

Felix Ellett

Yi Feng

Bruce D Levy

Moira K B Whyte

Stephen A Renshaw

Affiliations

Soon will be listed here.

Abstract

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 (PGE) that drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous PGE synthase gene reveals PGE as essential for neutrophil inflammation resolution. Furthermore, PGE 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 PGE and LXA (lipoxin A) in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease.

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