Increased Granzyme A Expression In Type II Pneumocytes of Patients With Severe COPD

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with increased numbers of CD8+ cytotoxic T lymphocytes (CTLs) in the lung, but the functional activity of CTLs remains unknown. Granzyme A (GrA) and B (GrB) are serine proteases considered to be important effector molecules of CTLs and natural killer (NK) cells. OBJECTIVE: To investigate protein and mRNA expression of GrA and GrB in peripheral lung tissue from COPD patients and control subjects with normal lung function. METHODS: Paraffin-embedded sections of surgical lung specimens from 22 patients with COPD (FEV1 22 % predicted, GOLD 4) and 15 controls (FEV1 108 % predicted) were immunostained for GrA and GrB, and semi-quantified on a 3-point scale. Messenger RNA expression in total lung, specific cell types enriched for by laser capture microdissection (LCM) and freshly isolated primary cells was determined by RT-PCR. MEASUREMENTS AND MAIN RESULTS: GrA and GrB immunoreactivity was observed in CD8+ CTLs and CD57+ NK cells, but also in type II pneumocytes and alveolar macrophages in both groups. Bronchiolar epithelium stained positive for GrA, but negative for GrB. These observations were confirmed by RT-PCR on total lung, LCM-enriched specific cell types and freshly isolated primary type II pneumocytes. The scores of GrA-expressing type II pneumocytes were significantly higher in COPD versus controls. CONCLUSIONS: GrA and GrB mRNA and protein are detectable in human lung tissue. GrA expression is increased in type II pneumocytes of patients with very severe COPD. These results indicate that GrA may be important in the development of COPD