A possible role for CD8(+) and non-CD8(+) cell granzyme B in early small airway wall remodelling in centrilobular emphysema

作者：Kim Won Dong^*; Chi Hyun Sook; Choe Kang Hyeon; Oh Yeon Mok; Lee Sang Do; Kim Kyu Rae; Yoo Kwang Ha; Ngan David A; Elliott W Mark; Granville David J; Sin Don D; Hogg James C

来源：Respirology, 2013, 18(4): 688-696.

DOI：10.1111/resp.12069

• CD8
• centrilobular emphysema
• chronic obstructive pulmonary disease
• granzyme B
• macrophage scavenger receptor

Background and objective CD8+ cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8+ T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B-positive cells in relation to CD8+ cells in the small airway walls of emphysema. Methods Antibodies against CD8 and granzyme B were used to identify CD8+ and granzyme B+ cells. Volume fraction (Vv) of CD8+ and granzyme B+ cells were quantitated by the point counting method in the small airways of 13 non-smoker control subjects and 46 emphysema patients (14 panlobular emphysema (PLE) and 32 centrilobular emphysema (CLE) lungs). Immunohistochemical detection of macrophage scavenger receptor was also performed in randomly selected cases. Results The Vv of CD8+ and granzyme B+ cells in CLE was greater than those in control and PLE (both P%26lt;0.001) subjects. The Vv of granzyme B+ cells was greater than that of CD8+ cells (P=0.006), and not all CD8+ cells were positive for granzyme B in CLE subjects. Monocytes expressing both granzyme B and macrophage scavenger receptor and granulocytes expressing granzyme B were identified. Conclusions Upregulation of granzyme B in CD8+ and non-CD8+ cells is an early phenomenon of small airway wall remodelling in centrilobular emphysema and suggests its possible role in the pathogenesis of COPD.

• 出版日期2013-5