Tuberc Respir Dis.  2020 Dec;83(Supple 1):S25-S33. 10.4046/trd.2020.0089.

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

Affiliations
  • 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

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.

Keyword

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