title: CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses.
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.
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Dyer
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pallas
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Medina-Ruiz
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schuette
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Gillian J
authors.initials: GJ
authors.lastname: Wilson
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham