CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses

Dyer, D. P. , Pallas, K., Medina Ruiz, L., Schuette, F., Wilson, G. J. and Graham, G. J. (2017) CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses. Scientific Reports, 7, 42681. (doi:10.1038/srep42681) (PMID:28205614) (PMCID:PMC5311995)

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Abstract

CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dyer, Dr Douglas and Pallas, Mr Kenny and Wilson, Dr Gillian and Schuette, Dr Fabian and Medina-Ruiz, Dr Laura and Graham, Professor Gerard
Authors: Dyer, D. P., Pallas, K., Medina Ruiz, L., Schuette, F., Wilson, G. J., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7:42681
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOME)099251/Z/12/ZIII -IMMUNOLOGY