Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by progressive and irreversible airway obstruction, and mainly caused by a chronic exposure to lung irritants. As of 2010, 384 million people suffered from COPD worldwide. It is widely accepted that a chronic inflammatory response is integral to COPD pathogenesis and linked to disease progression. The cellular mediators and molecular mechanisms of COPD-associated inflammation are not completely understood and are difficult to emulate in animal models, which hinders the development of better treatments. In this study, experimental COPD and its associated inflammation were induced in mice using a 4-week protocol involving intranasal administration of LPS and elastase. Model validation on wild-type mice yielded COPD-like disease judging from flow cytometric analyses with and pulmonary function testing. After 4 weeks of exposure to LPS and elastase, mice developed classic aspects of COPD such an increase in lung-infiltrating cells, (e.g. neutrophils, CD4+and CD8+ T-cells). Acute inflammation in the form of substantial neutrophilia was due to the last LPS administration, whereas the observed eosinophilia and elevated counts of mast cell populations, CD4+ and CD8+ T-cells were due to the cumulative effects of LPS and elastase. The nature of COPD-associated inflammation in mast cell deficient mice was investigated in two experiments. Our first experiment suggested a mild protective role of mast cells, a finding not reproduced in the second experiment possibly due to expired elastase. Our study suggests that mast cells are not required for COPD-associated inflammation.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-414963 |
| Date | January 2020 |
| Creators | Danielsson, Erik |
| Publisher | Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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