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Semaphorin 3F signaling actively retains neutrophils at sites of inflammation

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  • Suttida Eamsamarng
  • Stephen A. Renshaw
  • Patricia Coelho
  • Ananda S. Mirchandani
  • Jessie-may Morgan
  • Felix E. Ellett
  • Ximena L. Raffo-iraolagoitia
  • Catherine Loynes
  • Philip M. Elks
  • Freek Van Eeden
  • Leo M. Carlin
  • Andrew J. W. Furley

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http://www.jci.org/articles/view/130834
Original languageEnglish
JournalJournal of Clinical Investigation
Early online date19 Mar 2020
DOIs
Publication statusE-pub ahead of print - 19 Mar 2020

Abstract

Neutrophilic inflammation is central to disease pathogenesis, e.g. in chronic obstructive pulmonary disease, yet the mechanisms retaining neutrophils within tissues remain poorly understood. With emerging evidence that axon guidance
factors can regulate myeloid recruitment and that neutrophils can regulate expression of a class 3 Semaphorin, SEMA3F, we investigated the role of SEMA3F in inflammatory cell retention within inflamed tissues. We observed that neutrophils upregulate SEMA3F in response to pro-inflammatory mediators and following recruitment to the inflamed lung. In both zebrafish tail injury and murine acute lung injury models of neutrophilic inflammation, overexpression of SEMA3F delayed inflammation resolution with slower neutrophil migratory speeds and retention of neutrophils within the tissues.
Conversely, constitutive loss of sema3f accelerated egress of neutrophils from the tail injury site in fish, whilst neutrophil specific deletion of Sema3f in mice resulted in more rapid neutrophil transit through the airways, and significantly reduced time to resolution of the neutrophilic response. Study of filamentous- (F
-) actin subsequently showed SEMA3F mediated retention is associated with F-actin disassembly. In conclusion, SEMA3F signaling actively regulates neutrophil retention within the injured tissues with consequences for neutrophil clearance and inflammation resolution.

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