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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aspergillus fumigatus / immunology*
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Aspergillus fumigatus / pathogenicity
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Asthma / genetics
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Asthma / immunology*
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Asthma / microbiology
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Asthma / pathology
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Bronchial Hyperreactivity / chemically induced
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Bronchial Hyperreactivity / genetics
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Bronchial Hyperreactivity / immunology
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Bronchial Hyperreactivity / microbiology
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Bronchoalveolar Lavage Fluid / chemistry
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Cell Movement / immunology
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Chemokine CCL11
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Chemokine CCL4
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Chemokine CCL5 / metabolism
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Chemokine CXCL10
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Chemokines, CC / metabolism
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Chemokines, CXC / biosynthesis
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Chemokines, CXC / physiology
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Chronic Disease
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Disease Models, Animal
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Eosinophils / pathology
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Female
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Immunity, Innate / genetics
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Immunoglobulin E / biosynthesis
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Immunoglobulin E / blood
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis
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Interleukin-4 / metabolism
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Interleukin-5 / metabolism
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Macrophage Inflammatory Proteins / biosynthesis
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Macrophage Inflammatory Proteins / physiology
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Methacholine Chloride / administration & dosage
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Mice
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Mice, Knockout
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Neutrophils / pathology
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Peroxidase / metabolism
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Receptors, Interleukin-8B / deficiency
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Receptors, Interleukin-8B / genetics
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Receptors, Interleukin-8B / physiology*
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Spores, Fungal / immunology
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Spores, Fungal / pathogenicity
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T-Lymphocytes / pathology
Substances
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Ccl11 protein, mouse
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Chemokine CCL11
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CXCL10
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Chemokines, CC
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Chemokines, CXC
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Interleukin-5
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Macrophage Inflammatory Proteins
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Receptors, Interleukin-8B
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Methacholine Chloride
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Interleukin-12
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Interleukin-4
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Immunoglobulin E
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Interferon-gamma
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Peroxidase