Your browser doesn't support javascript.
loading
Adverse roles of mast cell chymase-1 in COPD.
Liu, Gang; Jarnicki, Andrew G; Paudel, Keshav R; Lu, Wenying; Wadhwa, Ridhima; Philp, Ashleigh M; Van Eeckhoutte, Hannelore; Marshall, Jacqueline E; Malyla, Vamshikrishna; Katsifis, Angelica; Fricker, Michael; Hansbro, Nicole G; Dua, Kamal; Kermani, Nazanin Z; Eapen, Mathew S; Tiotiu, Angelica; Chung, K Fan; Caramori, Gaetano; Bracke, Ken; Adcock, Ian M; Sohal, Sukhwinder S; Wark, Peter A; Oliver, Brian G; Hansbro, Philip M.
Afiliación
  • Liu G; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Jarnicki AG; Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Australia.
  • Paudel KR; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Lu W; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Australia.
  • Wadhwa R; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Philp AM; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Van Eeckhoutte H; St Vincent's Medical School, University of New South Wales Medicine, University of New South Wales, Sydney, Australia.
  • Marshall JE; Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Malyla V; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Katsifis A; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Fricker M; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Hansbro NG; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia.
  • Dua K; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Kermani NZ; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, Australia.
  • Eapen MS; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, Australia.
  • Tiotiu A; Data Science Institute, Department of Computing, Imperial College London, London, UK.
  • Chung KF; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Australia.
  • Caramori G; National Heart and Lung Institute, Imperial College London, London, UK.
  • Bracke K; Department of Pulmonology, University Hospital of Nancy, Nancy, France.
  • Adcock IM; National Heart and Lung Institute, Imperial College London, London, UK.
  • Sohal SS; UOC di Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina, Italy.
  • Wark PA; Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Oliver BG; National Heart and Lung Institute, Imperial College London, London, UK.
  • Hansbro PM; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Australia.
Eur Respir J ; 60(6)2022 12.
Article en En | MEDLINE | ID: mdl-35777766
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 (hCMA)1 and its orthologue mCMA1/mouse mast cell protease (mMCP)5 are exocytosed from activated mast cells 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 protease's role and potential for therapeutic targeting in CS-induced experimental COPD. In addition, we used ex vivo/in vitro studies to define mechanisms. RESULTS: The levels of hCMA1 mRNA and CMA1+ mast cells were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated mast cell numbers and mMCP5 protein were increased in lung tissues of wild-type 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 mast cells from wild-type, but not mmcp5 -/- mice with wild-type lung macrophages increased in tumour necrosis factor (TNF)-α release. It also caused the release of CMA1 from human mast cells, and recombinant hCMA-1 induced TNF-α 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-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfisema Pulmonar / Enfermedad Pulmonar Obstructiva Crónica / Enfisema Límite: Animals / Humans Idioma: En Revista: Eur Respir J Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfisema Pulmonar / Enfermedad Pulmonar Obstructiva Crónica / Enfisema Límite: Animals / Humans Idioma: En Revista: Eur Respir J Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido