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The Role of Granzyme B Containing Cells in the Progression of Chronic Obstructive Pulmonary Disease

Tuberculosis and Respiratory Diseases 2020년 83권 0호 p.25 ~ 33
김원동, 지현숙, 최강현, 김우성, Hogg James C., Sin Don D.,
소속 상세정보
김원동 ( Kim Won-Dong ) - University of Ulsan College of Medicine Asan Medical Center Department of Pulmonary and Critical Care Medicine
지현숙 ( Chi Hyun-Sook ) - University of Ulsan College of Medicine Asan Medical Center Department of Laboratory Medicine
최강현 ( Choe Kang-Hyeon ) - Chungbuk National University College of Medicine Department of Internal Medicine
김우성 ( Kim Woo-Sung ) - University of Ulsan College of Medicine Asan Medical Center Department of Pulmonary and Critical Care Medicine
 ( Hogg James C. ) - University of British Columbia St. Paul’s Hospital James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research
 ( Sin Don D. ) - University of British Columbia St. Paul’s Hospital James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research

Abstract


Background: Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain 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.

Methods: GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (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.

Results: The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1.

Conclusion: 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.

키워드

Chronic Obstructive Pulmonary Disease; Granzyme B Positive Cell; CD8+ T Cell; Centrilobular Emphysema; Regulatory Cells

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