Decreased macrophage release of TGF-b and TIMP-1 in chronic obstructive

ABSTRACT: The present study tested the hypothesis that alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) release more pro-inflammatory and/ or less anti-inflammatory mediators than those from smokers with normal lung function and never-smokers. AM were sorted by flow cytometry from bronchoalveolar lavage fluid in 13 patients with COPD (mean¡SEM 67¡2 yrs, forced expiratory volume in one second (FEV1) 61¡4 % reference), 16 smokers with normal lung function (55¡2 yrs, FEV1 97¡4 % reference) and seven never-smokers (67¡7 yrs, FEV1 94¡4 % reference). After sorting, AM were cultured (with and without lipopolysaccharide stimulation) after 4 h and 24 h, and the concentrations of leukotriene B4 (LTB4), transforming growth factor (TGF)-b1 and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in freshly isolated AM was determined by flow cytometry. LTB4 secretion and ROI production were not different between groups. In contrast, AM from COPD patients released significantly less TGF-b1 and TIMP-1 than those from smokers with normal lung function and nonsmokers. In conclusion, these observations are compatible with reduced anti-inflammatory and anti-elastolytic capacity in chronic obstructive pulmonary disease, which is likely to contribute to the pathogenesis of the disease