Grant: Travel Awards - Institute Community Support

Chronic obstructive pulmonary disorder (COPD) is a lung condition characterized by prolonged inflammation due to unregulated inflammatory signalling in immune cells such as macrophages. Proteases, Cathepsin S (CatS) and Cathepsin L (CatL), whose function is to cut other proteins, are found to be highly expressed in patients with COPD and their degradative activity within macrophages has been correlated with the development of COPD. Different macrophage populations in the lung, including alveolar and interstitial macrophages, have unique roles in COPD inflammatory networks however the action of CatS and CatL in each corresponding macrophage population has not yet been fully characterized. We hypothesize that cathepsins have widely different repertoires of proteins they cut within macrophages. Macrophages from mice lacking cathepsins were first compared to obtain a baseline protease cleavage profile for CatS and CatL. Using terminal amine isotopic labelling of substrates (TAILS), a technique to study what proteases cut, we identified unique candidates cut by different cathepsins. These include vimentin, and tumor-necrosis factor receptor II (TNF-RII). Furthermore, these results suggest that CatL primarily performs limited degradation (processing) while CatS performs multiple cuts (digest) on its substrates. In conclusion, our large scale analysis data have shown that some macrophage populations subjected to inflammation had different profiles with high similarity of candidates including vimentin and TNF-RII. We aim to establish a signatures of candidates to be validated in a COPD model and extend our findings to investigate human COPD patient's sputum at exacerbation and recovery.