Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease
- Author
- Gang Liu, Andrew G Jarnicki, Keshav R Paudel, Wenying Lu, Ridhima Wadhwa, Ashleigh M Philp, Hannelore Van Eeckhoutte (UGent) , Jacqueline E Marshall, Vamshikrishna Malyla, Angelica Katsifis, Michael Fricker, Nicole G Hansbro, Kamal Dua, Nazanin Z Kermani, Mathew S Eapen, Angelica Tiotiu, K Fan Chung, Gaetano Caramori, Ken Bracke (UGent) , Ian M Adcock, Sukhwinder S Sohal, Peter A Wark, Brian G Oliver and Philip M Hansbro
- Organization
- Abstract
- BACKGROUND: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase-1 (hCMA1) and it's ortholog mCMA1/mouse mast cell (MC) protease-5 (mMCP5) are exocytosed from activated MCs and have adverse roles in numerous disorders, but their role in COPD is unknown.; METHODS: We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5-deficient (-/-) mice to evaluate this proteases' role and potential for therapeutic targeting in CS-induced experimental COPD. We also used ex vivo/in vitro studies to define mechanisms.; RESULTS: The levels of hCMA1 mRNA and CMA1+ MCs were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated MC numbers and mMCP5 protein were increased in lung tissues of wild-type (WT) mice with experimental COPD. mmcp5 -/- mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of MCs from WT but not mmcp5 -/- mice with WT lung macrophages increased in TNF-alpha release. It also caused the release of CMA1 from human MCs, and recombinant hCMA-1 induced TNF-alpha release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.; CONCLUSION: CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-alpha expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD. Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GJ2QRWEVZS5MW9BW2MH0CCT6
- MLA
- Liu, Gang, et al. “Adverse Roles of Mast Cell Chymase-1 in Chronic Obstructive Pulmonary Disease.” EUROPEAN RESPIRATORY JOURNAL, vol. 60, no. 6, 2022, doi:10.1183/13993003.01431-2021.
- APA
- Liu, G., Jarnicki, A. G., Paudel, K. R., Lu, W., Wadhwa, R., Philp, A. M., … Hansbro, P. M. (2022). Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease. EUROPEAN RESPIRATORY JOURNAL, 60(6). https://doi.org/10.1183/13993003.01431-2021
- Chicago author-date
- Liu, Gang, Andrew G Jarnicki, Keshav R Paudel, Wenying Lu, Ridhima Wadhwa, Ashleigh M Philp, Hannelore Van Eeckhoutte, et al. 2022. “Adverse Roles of Mast Cell Chymase-1 in Chronic Obstructive Pulmonary Disease.” EUROPEAN RESPIRATORY JOURNAL 60 (6). https://doi.org/10.1183/13993003.01431-2021.
- Chicago author-date (all authors)
- Liu, Gang, Andrew G Jarnicki, Keshav R Paudel, Wenying Lu, Ridhima Wadhwa, Ashleigh M Philp, Hannelore Van Eeckhoutte, Jacqueline E Marshall, Vamshikrishna Malyla, Angelica Katsifis, Michael Fricker, Nicole G Hansbro, Kamal Dua, Nazanin Z Kermani, Mathew S Eapen, Angelica Tiotiu, K Fan Chung, Gaetano Caramori, Ken Bracke, Ian M Adcock, Sukhwinder S Sohal, Peter A Wark, Brian G Oliver, and Philip M Hansbro. 2022. “Adverse Roles of Mast Cell Chymase-1 in Chronic Obstructive Pulmonary Disease.” EUROPEAN RESPIRATORY JOURNAL 60 (6). doi:10.1183/13993003.01431-2021.
- Vancouver
- 1.Liu G, Jarnicki AG, Paudel KR, Lu W, Wadhwa R, Philp AM, et al. Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease. EUROPEAN RESPIRATORY JOURNAL. 2022;60(6).
- IEEE
- [1]G. Liu et al., “Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease,” EUROPEAN RESPIRATORY JOURNAL, vol. 60, no. 6, 2022.
@article{01GJ2QRWEVZS5MW9BW2MH0CCT6, abstract = {{BACKGROUND: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase-1 (hCMA1) and it's ortholog mCMA1/mouse mast cell (MC) protease-5 (mMCP5) are exocytosed from activated MCs and have adverse roles in numerous disorders, but their role in COPD is unknown.; METHODS: We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5-deficient (-/-) mice to evaluate this proteases' role and potential for therapeutic targeting in CS-induced experimental COPD. We also used ex vivo/in vitro studies to define mechanisms.; RESULTS: The levels of hCMA1 mRNA and CMA1+ MCs were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated MC numbers and mMCP5 protein were increased in lung tissues of wild-type (WT) mice with experimental COPD. mmcp5 -/- mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of MCs from WT but not mmcp5 -/- mice with WT lung macrophages increased in TNF-alpha release. It also caused the release of CMA1 from human MCs, and recombinant hCMA-1 induced TNF-alpha release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.; CONCLUSION: CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-alpha expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD. Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.}}, articleno = {{2101431}}, author = {{Liu, Gang and Jarnicki, Andrew G and Paudel, Keshav R and Lu, Wenying and Wadhwa, Ridhima and Philp, Ashleigh M and Van Eeckhoutte, Hannelore and Marshall, Jacqueline E and Malyla, Vamshikrishna and Katsifis, Angelica and Fricker, Michael and Hansbro, Nicole G and Dua, Kamal and Kermani, Nazanin Z and Eapen, Mathew S and Tiotiu, Angelica and Chung, K Fan and Caramori, Gaetano and Bracke, Ken and Adcock, Ian M and Sohal, Sukhwinder S and Wark, Peter A and Oliver, Brian G and Hansbro, Philip M}}, issn = {{0903-1936}}, journal = {{EUROPEAN RESPIRATORY JOURNAL}}, language = {{eng}}, number = {{6}}, pages = {{16}}, title = {{Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease}}, url = {{http://doi.org/10.1183/13993003.01431-2021}}, volume = {{60}}, year = {{2022}}, }
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