Macrophage/epithelial cell CCL2 contributes to rhinovirus-induced hyperresponsiveness and inflammation in a mouse model of allergic airways disease
| العنوان: | Macrophage/epithelial cell CCL2 contributes to rhinovirus-induced hyperresponsiveness and inflammation in a mouse model of allergic airways disease |
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| المؤلفون: | Christina L. McHenry, Emily R. Bowman, J. Kelley Bentley, Marc B. Hershenson, Jun Young Hong, Toby C. Lewis, Yutein Chung, Dina Schneider, Deepti R. Nagarkar, Adam M. Goldsmith |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 304:L162-L169 |
| بيانات النشر: | American Physiological Society, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Rhinovirus, Ovalbumin, Physiology, Antigens, Differentiation, Myelomonocytic, Gene Expression, Inflammation, CCL2, medicine.disease_cause, Mice, Th2 Cells, Antigens, CD, Physiology (medical), Hypersensitivity, medicine, Animals, Humans, Macrophage, Chemokine CCL7, Chemokine CCL4, Child, Lung, Chemokine CCL2, Interleukin 4, Chemokine CCL20, Interleukin-13, biology, Macrophages, Epithelial Cells, Articles, Cell Biology, respiratory system, Antibodies, Neutralizing, respiratory tract diseases, Disease Models, Animal, medicine.anatomical_structure, Interleukin 13, Immunology, biology.protein, Chemokine CCL19, Interleukin-4, medicine.symptom, circulatory and respiratory physiology |
| الوصف: | Human rhinovirus (HRV) infections lead to exacerbations of lower airways disease in asthmatic patients but not in healthy individuals. However, underlying mechanisms remain to be completely elucidated. We hypothesized that the Th2-driven allergic environment enhances HRV-induced CC chemokine production, leading to asthma exacerbations. Ovalbumin (OVA)-sensitized and -challenged mice inoculated with HRV showed significant increases in the expression of lung CC chemokine ligand (CCL)-2/monocyte chemotactic protein (MCP)-1, CCL4/macrophage inflammatory protein (MIP)-1β, CCL7/MCP-3, CCL19/MIP-3β, and CCL20/MIP3α compared with mice treated with OVA alone. Inhibition of CCL2 with neutralizing antibody significantly attenuated HRV-induced airways inflammation and hyperresponsiveness in OVA-treated mice. Immunohistochemical stains showed colocalization of CCL2 with HRV in epithelial cells and CD68-positive macrophages, and flow cytometry showed increased CCL2+, CD11b+cells in the lungs of OVA-treated, HRV-infected mice. Compared with lung macrophages from naïve mice, macrophages from OVA-exposed mice expressed significantly more CCL2 in response to HRV infection ex vivo. Pretreatment of mouse lung macrophages and BEAS-2B human bronchial epithelial cells with interleukin (IL)-4 and IL-13 increased HRV-induced CCL2 expression, and mouse lung macrophages from IL-4 receptor knockout mice showed reduced CCL2 expression in response to HRV, suggesting that exposure to these Th2 cytokines plays a role in the altered HRV response. Finally, bronchoalveolar macrophages from children with asthma elaborated more CCL2 upon ex vivo exposure to HRV than cells from nonasthmatic patients. We conclude that CCL2 production by epithelial cells and macrophages contributes to HRV-induced airway hyperresponsiveness and inflammation in a mouse model of allergic airways disease and may play a role in HRV-induced asthma exacerbations. |
| تدمد: | 1522-1504 1040-0605 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43fa1e9a7ec617f6529947637d1f1095 https://doi.org/10.1152/ajplung.00182.2012 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....43fa1e9a7ec617f6529947637d1f1095 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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