Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Program in Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Augusta, GA, 30901, USA.
Respir Res. 2020 Jul 16;21(1):188. doi: 10.1186/s12931-020-01446-5.
A 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.
ADAM15 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 1 s (FEV), ratio of FEV to forced vital capacity (FEV/FVC), and pack-years of smoking history.
ADAM15 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 α-smooth muscle (α-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 FEV and FEV/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.
These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.
解整合素金属蛋白酶域 15（ADAM15）在体外由激活的白细胞和成纤维细胞表达。ADAM15 的表达是否在 COPD 患者的肺部增加尚不清楚。
测量 COPD 患者、吸烟者和非吸烟者的全肺和支气管肺泡灌洗液（BAL）巨噬细胞样本中的 ADAM15 基因表达和/或蛋白水平。测量 COPD 患者和对照者 BAL 液（BALF）和血浆样本中的可溶性 ADAM15 蛋白水平。使用免疫染色鉴定肺部表达 ADAM15 的细胞。肺部不同细胞中的 ADAM15 染色与 1 秒用力呼气量（FEV）、FEV 与用力肺活量（FEV/FVC）的比值和吸烟史的包年数相关。
与吸烟者和非吸烟者相比，ADAM15 基因表达和/或蛋白水平在肺泡巨噬细胞和 COPD 患者的全肺样本中增加。COPD 患者和对照者的 BALF 和血浆样本中的可溶性 ADAM15 蛋白水平相似。COPD 患者肺部的巨噬细胞、CD8 T 细胞、上皮细胞和气道α-平滑肌（α-SMA）阳性细胞中的 ADAM15 免疫染色增加。巨噬细胞、CD8 T 细胞和支气管（而非肺泡）上皮细胞中的 ADAM15 免疫染色与 FEV 和 FEV/FVC 呈负相关，但与吸烟史的包年数无关。气道α-SMA 阳性细胞中的 ADAM15 染色水平与 FEV/FVC 直接相关。在 THP-1 细胞中过表达 ADAM15 可减少其释放的基质金属蛋白酶和 CCL2。
这些结果将 ADAM15 表达的增加，特别是在肺部白细胞和支气管上皮细胞中的表达，与 COPD 的发病机制联系起来。
