A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD
| Autor: | Jay C. Horvat, Julia Aniscenko, Nathan W. Bartlett, Philip M. Hansbro, Rebecca M. Pearson, Aran Singanayagam, Nicholas Glanville, Sebastian L. Johnston, James W. Pinkerton, Ross P. Walton |
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| Přispěvatelé: | Wellcome Trust |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Chemokine Time Factors Exacerbation Rhinovirus MPO myeloperoxidase Research & Experimental Medicine Inflammatory responses TNF tumour necrosis factor IP-10 interferon γ-induced protein 10 Experimental emphysema FRC functional residual capacity Pulmonary Disease Chronic Obstructive exacerbation Medicine Obstructive pulmonary-disease COPD biology Haemophilus-influenzae General Medicine 11 Medical And Health Sciences S10 AHR airway hyper-responsiveness CXCL10 C-X-C motif chemokine 10 Medicine Research & Experimental H&E haematoxylin and eosin LPS lipopolysaccharide Tumor necrosis factor alpha Female BAL bronchoalveolar lavage medicine.symptom Chemokines Life Sciences & Biomedicine CCL5 chemokine (C-C motif) ligand 5 Inflammation MIP-2 macrophage inflammatory protein 2 S8 RANTES regulated on activation normal T-cell expressed and secreted CCL5 Proinflammatory cytokine chronic obstructive pulmonary disease PAS periodic acid–Schiff CXCL10 Animals IFN interferon mouse models Original Paper Science & Technology Picornaviridae Infections business.industry TLC total lung capacity medicine.disease RV rhinovirus Asthma IL interleukin Airway epithlial-cells Mice Inbred C57BL Disease Models Animal COPD chronic obstructive pulmonary disease Cardiovascular System & Hematology inflammation Immunology biology.protein PFA paraformaldehyde business |
| Zdroj: | Clinical Science (London, England : 1979) |
| Popis: | Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infections, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis. We aimed to develop a short-term mouse model that reproduced the hallmark features of RV-induced exacerbation of COPD. Evaluation of complex protocols involving multiple dose elastase and lipopolysaccharide (LPS) administration combined with RV1B infection showed suppression rather than enhancement of inflammatory parameters compared with control mice infected with RV1B alone. Therefore, these approaches did not accurately model the enhanced inflammation associated with RV infection in patients with COPD compared with healthy subjects. In contrast, a single elastase treatment followed by RV infection led to heightened airway neutrophilic and lymphocytic inflammation, increased expression of tumour necrosis factor (TNF)-α, C-X-C motif chemokine 10 (CXCL10)/IP-10 (interferon γ-induced protein 10) and CCL5 [chemokine (C-C motif) ligand 5]/RANTES (regulated on activation, normal T-cell expressed and secreted), mucus hypersecretion and preliminary evidence for increased airway hyper-responsiveness compared with mice treated with elastase or RV infection alone. In summary, we have developed a new mouse model of RV-induced COPD exacerbation that mimics many of the inflammatory features of human disease. This model, in conjunction with human models of disease, will provide an essential tool for studying disease mechanisms and allow testing of novel therapies with potential to be translated into clinical practice. The present study describes a new short-term mouse model of rhinovirus (RV)-induced exacerbation of COPD (chronic obstructive pulmonary disease) which will facilitate insight into disease mechanisms and could provide a more efficient tool to test novel therapies with potential to be translated into clinical practice. |
| Databáze: | OpenAIRE |
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