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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Smoking and Nicotine Detoxification | Research

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: Xiaoyun Wang, Duo Zhang, Andrew Higham, Sophie Wolosianka, Xiaoyan Gai, Lu Zhou, Hans Petersen, Victor Pinto-Plata, Miguel Divo, Edwin K. Silverman, Bartolome Celli, Dave Singh, Yongchang Sun, Caroline A. Owen

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

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.

Methods

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 (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history.

Results

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 FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.

Conclusions

These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.
Appendix
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Metadata
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
Xiaoyun Wang
Duo Zhang
Andrew Higham
Sophie Wolosianka
Xiaoyan Gai
Lu Zhou
Hans Petersen
Victor Pinto-Plata
Miguel Divo
Edwin K. Silverman
Bartolome Celli
Dave Singh
Yongchang Sun
Caroline A. Owen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01446-5

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