Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages
| Autor: | Marisa J. Linn, Christina L. McHenry, Emily R. Bowman, Umadevi S. Sajjan, Marc B. Hershenson, J. Kelley Bentley, Ying Zhao, Jee Shim, Babina Gosangi, Qiong Wang, Deepti R. Nagarkar, Dina Schneider, Wan C. Tsai, Nicholas W. Lukacs |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Eotaxin
Chemokine CCL11 Rhinovirus Ovalbumin Immunology Antigens Differentiation Myelomonocytic Inflammation medicine.disease_cause Article Mice Antigens CD Macrophages Alveolar medicine Immunology and Allergy Macrophage Eosinophilia Animals Humans Lung CCL11 Mice Inbred BALB C Microscopy Confocal Picornaviridae Infections biology Reverse Transcriptase Polymerase Chain Reaction respiratory system Immunohistochemistry respiratory tract diseases Eosinophils medicine.anatomical_structure biology.protein Cytokines medicine.symptom Bronchial Hyperreactivity Inflammation Mediators HeLa Cells |
| Popis: | Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus (RV)-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated OVA-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared with sham-infected, OVA-treated mice, virus-infected mice showed increased lung infiltration with neutrophils, eosinophils and macrophages, airway cholinergic hyperresponsiveness, and increased lung expression of cytokines including eotaxin-1/CCL11, IL-4, IL-13, and IFN-γ. Administration of anti–eotaxin-1 attenuated rhinovirus-induced airway eosinophilia and responsiveness. Immunohistochemical analysis showed eotaxin-1 in the lung macrophages of virus-infected, OVA-treated mice, and confocal fluorescence microscopy revealed colocalization of rhinovirus, eotaxin-1, and IL-4 in CD68-positive cells. RV inoculation of lung macrophages from OVA-treated, but not PBS-treated, mice induced expression of eotaxin-1, IL-4, and IL-13 ex vivo. Macrophages from OVA-treated mice showed increased expression of arginase-1, Ym-1, Mgl-2, and IL-10, indicating a shift in macrophage activation status. Depletion of macrophages from OVA-sensitized and -challenged mice reduced eosinophilic inflammation and airways responsiveness following RV infection. We conclude that augmented airway eosinophilic inflammation and hyperresponsiveness in RV-infected mice with allergic airways disease is directed in part by eotaxin-1. Airway macrophages from mice with allergic airways disease demonstrate a change in activation state characterized in part by altered eotaxin and IL-4 production in response to RV infection. These data provide a new paradigm to explain RV-induced asthma exacerbations. |
| Databáze: | OpenAIRE |
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