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DOI:    [Accepted]
Published online October 20, 2020.
The Role of Granzyme B Containing Cells in the Progression of Chronic Obstructive Pulmonary Disease
Won-Dong Kim, M.D.1, Hyun-Sook Chi, M.D.2, Kang-Hyeon Choe, M.D.3, Woo-Sung Kim, M.D.1, James C. Hogg, M.D.4, Don D. Sin, M.D.4
1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
2Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
3Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
4The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Correspondence:  Won-Dong Kim, Tel: 82-10-8880-4491, Fax: 82-2-6083-4087, 
Received: 6 August 2020   • Revised: 13 September 2020   • Accepted: 20 October 2020
Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remains unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD.
GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 non-smoking control, 12 panlobular (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject.
The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05, p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and FEV1 (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1.
Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.
Key Words: Chronic obstructive pulmonary disease, Granzyme B, CD8+ T cell, Centrilobular emphysema, Regulatory cells

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