title: CXCR2 is necessary for the development and persistence of chronic fungal asthma in mice.
abstract: The role of CXCR during allergic airway and asthmatic diseases is yet to be fully characterized. Therefore, the present study addressed the role of CXCR2 during Aspergillus fumigatus-induced asthma. Mice deficient in CXCR2 (CXCR2-/-) and wild-type counterparts (CXCR2+/+) were sensitized to A. fumigatus Ags and challenged with A. fumigatus conidia, and the resulting allergic airway disease was monitored for up to 37 days. At days 3 and 7 after conidia, CXCR2-/- mice exhibited significantly greater methacholine-induced airway hyperreactivity than did CXCR2+/+ mice. In contrast, CXCR2-deficient mice exhibited significantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia. At all times after conidia, whole lung levels of IL-4, IL-5, and eotaxin/CC chemokine ligand 11 were significantly lower in CXCR2-/- mice than in the wild-type controls. Eosinophil and T cell, but not neutrophil, recruitment into the airways of A. fumigatus-sensitized CXCR2-/- mice was significantly impaired compared with wild-type controls at all times after the conidia challenge. Whole lung levels of IFN-gamma, inflammatory protein-10/CXC ligand (CXCL) 10, and monokine induced by IFN-gamma (MIG)/CXCL9 were significantly increased in CXCR2-/- mice compared with CXCR2+/+ mice at various times after conidia. Interestingly, at day 3 after conidia, neutrophil recruitment and airway hyperresponsiveness in CXCR2-/- mice was mediated by inflammatory protein-10/CXCL10 and, to a lesser degree, MIG/CXCL9. Taken together, these data suggest that CXCR2 contributes to the persistence of asthmatic disease due to A. fumigatus.
authors.affiliation: Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Schuh
authors.forename: Kate
authors.initials: K
authors.lastname: Blease
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000276:immunology; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000502:physiology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013172:Spores, Fungal / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D023063:Receptors, Interleukin-8B; D016210:Methacholine Chloride; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D009195:Peroxidase