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Annexins A1 and A2 as potential biomarkers of stress and respiratory disease susceptibility

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dc.contributor.advisor Caswell, Jeff
dc.contributor.author Senthilkumaran, Chandrika
dc.date.accessioned 2013-08-28T13:56:49Z
dc.date.available 2013-08-28T13:56:49Z
dc.date.copyright 2013-08
dc.date.created 2013-08-12
dc.date.issued 2013-08-28
dc.identifier.uri http://hdl.handle.net/10214/7427
dc.description.abstract This study investigated proteomic changes in bronchoalveolar lavage fluid (BALF) of beef calves to identify alterations related to development of naturally occurring bovine respiratory disease. BALF was collected from 162 healthy beef calves soon after weaning and transportation. Two-dimensional gel electrophoresis and mass spectrometric analysis revealed calves that later developed pneumonia had significantly lower levels of anti-inflammatory proteins including annexin A1, RAGE-binding protein, apolipoprotein-A, heat shock protein beta-1 and thioredoxin, but higher levels of antioxidant and pro-inflammatory proteins such as immunoglobulin light chain variable region, cyclophilin A, serum albumin precursor and glutathione S-transferase P. Difference in gel electrophoresis-based analysis further showed lower levels of annexin A1, annexin A2, peroxiredoxin I, calycyphosin, superoxide dismutase, macrophage capping protein and dihydrodiol dehydrogenase 3 in the calves that later developed pneumonia. Differences in annexin levels were partially confirmed by Western blot analysis. In healthy calves, immunohistochemistry revealed cytoplasmic expression of annexin A1 in surface epithelium of large airways, tracheobronchial submucosal glands, and goblet cells, and to a lesser degree in small airways but not in alveolar epithelium. Flow cytometry and immunocytochemistry labeled annexin A1 in blood and bronchoalveolar lavage neutrophils, monocytes, macrophages and lymphocytes. Annexin A2 expression was detected in surface epithelium of small airways, some mucosal lymphocytes, and endothelium, with weak expression in large airways, tracheobronchial submucosal glands and alveolar epithelium. For both proteins, the level of expression was similar in tissues collected 5 days after intrabronchial challenge with M. haemolytica compared to that from sham-inoculated calves. A sandwich ELISA for annexin A1 was developed. For use with BALF, the working range was 0.3-317 ng/ml and the sensitivity was 0.8 ng/ml. The coefficient of variation of intra-assay and the between assays was less than 20%. Together, these findings reveal annexins A1 and A2 as promising biomarkers of susceptibility to BRD in healthy at-risk calves. Further, the anti-inflammatory and pro-resolving functions of these proteins suggest roles in the pathogenesis of bacterial pneumonia of feedlot cattle. en_US
dc.description.sponsorship Natural Sciences and Engineering Council (NSERC), Ontario Cattlemen’s Association, Ontario Ministry of Agriculture and Food and Ontario Veterinary College Fellowship Program en_US
dc.language.iso en en_US
dc.subject biomarkers en_US
dc.subject stress en_US
dc.subject respiratory disease susceptibility en_US
dc.subject beef calves en_US
dc.subject Annexins A1 and A2 en_US
dc.subject gel electrophoresis-based analysis en_US
dc.subject bronchoalveolar lavage fluid (BALF) en_US
dc.subject weaning en_US
dc.subject transportation en_US
dc.title Annexins A1 and A2 as potential biomarkers of stress and respiratory disease susceptibility en_US
dc.type Thesis en_US
dc.degree.programme Pathobiology en_US
dc.degree.name Doctor of Philosophy en_US
dc.degree.department Department of Pathobiology en_US
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