Decreased release of TIMP-1 and TGF-β in cultured alveolar macrophages of patients with chronic obstructive pulmonary disease
J. Sauleda, A. Noguera, A. R. Pons, J. Pons, B. Barcelo, A. Fuster, A. G. N. Agusti (Palma Mallorca, Spain)
Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Airway diseases
Abstract There is increasing evidence that alveolar macrophages (AM) play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study we determined (by ELISA) the concentration of several inflammatory mediators (TIMP-1, MMP-9, TGF-β and LTB4) released by cultured AM (at 4 and 24 hours, with and without LPS stimulation) obtained from bronchoalveolar lavage samples in 17 COPD patients (65±2 yrs, 59±5 pack-yr, FEV1 56±4% ref, x±SEM), 17 smokers with normal lung function (55±2 yrs, 42±4 pack-yr, FEV1 97±4% ref) and 7 never smokers (67±7 yrs, FEV1 94±4% ref). Results show that: (1) TIMP-1 (ng/ml) and TGF-β (pg/ml) levels were lower in COPD patients (p<0.05) than in the other two groups (Table 1); (2) MMP-9 and LTB4 levels were similar in all groups (data not shown).
Table 1 COPD SMOKERS NON SMOKERS 4 hours 24 hours 4 hours 24 hours 4 hours 24 hours TIMP1 baseline 1.7±0.4 4.2±2.1 5.7±2 28.3±10.9 10±3 69.5±17.6 TIMP1 (LPS) 2.4±0.8 6.9±4.9 7.4±2.6 33.5±12.2 15.2±4.7 73±24.2 TGFβ baseline ND 17±5 ND 25.9±6.6 ND 13.9±5.1 TGFβ (LPS) ND 67±13 ND 109.6±10.4 ND 135±54.5
ND: Not detectable These results show that AM harvested from patients with COPD release less antielastolytic and anti-inflammatory mediators than smokers and never smokers with normal lung function. Funded in part by SEPAR 2000 and CICYT (SAF2001-0302) and ABEMAR.
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J. Sauleda, A. Noguera, A. R. Pons, J. Pons, B. Barcelo, A. Fuster, A. G. N. Agusti (Palma Mallorca, Spain). Decreased release of TIMP-1 and TGF-β in cultured alveolar macrophages of patients with chronic obstructive pulmonary disease. Eur Respir J 2003; 22: Suppl. 45, 1491
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