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J Cell Biol. 2014 Dec 8;207(5):589-98. doi: 10.1083/jcb.201408090.

Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration.

Author information

1
Departments of Pediatrics and Medical Microbiology and Immunology, Microbiology Doctoral Training Program and Medical Scientist Training Program, Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706.
2
Departments of Pediatrics and Medical Microbiology and Immunology, Microbiology Doctoral Training Program and Medical Scientist Training Program, Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706 Departments of Pediatrics and Medical Microbiology and Immunology, Microbiology Doctoral Training Program and Medical Scientist Training Program, Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706.
3
Departments of Pediatrics and Medical Microbiology and Immunology, Microbiology Doctoral Training Program and Medical Scientist Training Program, Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706 Huttenlocher@wisc.edu.

Abstract

Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK signaling in epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. We found that redox-SFK signaling through p22phox and Yes-related kinase is necessary for macrophage wound attraction and the subsequent reverse migration of neutrophils. Importantly, macrophage-specific reconstitution of p22phox revealed that macrophage redox signaling is necessary for neutrophil reverse migration. Thus, redox-SFK signaling in adjacent tissues is essential for coordinated leukocyte wound attraction and repulsion through pathways that involve contact-mediated guidance.

PMID:
25488917
PMCID:
PMC4259815
DOI:
10.1083/jcb.201408090
[Indexed for MEDLINE]
Free PMC Article

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