| Title | ADAM15 expression is increased in lung CD8(+) T cells, macrophages, and bronchial epithelial cells in patients with COPD and is inversely related to airflow obstruction |
| Authors | Wang, Xiaoyun Zhang, Duo Higham, Andrew Wolosianka, Sophie Gai, Xiaoyan Zhou, Lu Petersen, Hans Pinto-Plata, Victor Divo, Miguel Silverman, Edwin K. Celli, Bartolome Singh, Dave Sun, Yongchang Owen, Caroline A. |
| Affiliation | Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA Univ Georgia, Coll Pharm, Dept Clin & Adm Pharm, Program Clin & Expt Therapeut, Augusta, GA 30901 USA Augusta Univ, Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA Univ Manchester, Manchester Univ NHS Fdn Trust, Med Evaluat Unit, Manchester, Lancs, England Peking Univ, Dept Pulm & Crit Care Med, Hosp 3, Beijing, Peoples R China Lovelace Resp Res Inst, Albuquerque, NM 87108 USA Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA Harvard Med Sch, Boston, MA 02115 USA |
| Keywords | SMOKE-INDUCED EMPHYSEMA PULMONARY-DISEASE INFLAMMATION ADAM-15 FAMILY DISINTEGRIN METALLOPROTEINASES DESTRUCTION FIBROBLASTS APOPTOSIS |
| Issue Date | 16-Jul-2020 |
| Publisher | RESPIRATORY RESEARCH |
| Abstract | BackgroundA disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known.MethodsADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history.ResultsADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8(+) T cells, epithelial cells, and airway alpha -smooth muscle (alpha -SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8(+) T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway alpha -SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.ConclusionsThese results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD. |
| URI | http://hdl.handle.net/20.500.11897/590568 |
| DOI | 10.1186/s12931-020-01446-5 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
