Advanced search
1 file | 3.47 MB Add to list
Author
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.

Downloads

  • Liu et al, Eur Respir J 2022.pdf
    • full text (Accepted manuscript)
    • |
    • open access
    • |
    • PDF
    • |
    • 3.47 MB

Citation

Please use this url to cite or link to this publication:

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}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: