A Disintegrin and Metalloproteinase Domain-8: A Novel Protective Proteinase in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine
Francesca PolverinoCaroline A Owen

Abstract

ADAM8 (a disintegrin and metalloproteinase domain-8) is expressed by leukocytes and epithelial cells in health, but its contribution to the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. To determine whether the expression of ADAM8 is increased in the lungs of patients with COPD and cigarette smoke (CS)-exposed mice, and whether ADAM8 promotes the development of COPD. ADAM8 levels were measured in lung, sputum, plasma, and/or BAL fluid samples from patients with COPD, smokers, and nonsmokers, and wild-type (WT) mice exposed to CS versus air. COPD-like lung pathologies were compared in CS-exposed WT versus Adam8-/- mice. ADAM8 immunostaining was reduced in macrophages, and alveolar and bronchial epithelial cells in the lungs of patients with COPD versus control subjects, and CS- versus air-exposed WT mice. ADAM8 levels were similar in plasma, sputum, and BAL fluid samples from patients with COPD and control subjects. CS-exposed Adam8-/- mice had greater airspace enlargement and airway mucus cell metaplasia than WT mice, but similar small airway fibrosis. CS-exposed Adam8-/- mice had higher lung macrophage counts, oxidative stress levels, and alveolar septal cell death rates, but lower alveolar septal ce...Continue Reading

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Citations

Apr 26, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoyun WangCaroline A Owen
Mar 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shoji SuzukiTomoko Betsuyaku
Jul 17, 2018·American Journal of Respiratory and Critical Care Medicine·Josalyn L Cho, Benjamin D Medoff
Apr 9, 2019·American Journal of Respiratory and Critical Care Medicine·Wassim W LabakiSurya P Bhatt
Feb 5, 2021·Frontiers in Medicine·Francesca Polverino, Farrah Kheradmand
Aug 25, 2021·BMC Pulmonary Medicine·M TomchaneyF Polverino
May 26, 2021·American Journal of Respiratory and Critical Care Medicine·Francesca PolverinoBartolome Celli
Sep 4, 2019·Respiration; International Review of Thoracic Diseases·Stephan F van Eeden, James C Hogg

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biopsy
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nuclear translocation

Software Mentioned

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FlexiVent
MetaMorph

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