Increased Alveolar Plasminogen Activator in Early Asbestosis

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Abstract
Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure to the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of valveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity weremeasured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 .+-. 17.3 versus 41.1 .+-. 7.2 U/105 AM-24 h, p < 0.05) as was the BAL fluid PA activity (674.9 .+-. 168.4 versus 81.3 .+-. 19.7 U/mg alb-24 h, p < 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p < 0.005), AM PA activity (p < 0.02), and BAL PA activity (p < 0.001) compared to the control group. BAL fluid PA activity was also assessed in 30 workers exposed to asbestos in the mines and mills of the Eastern Townships of Quebec for an average duration of 33 .+-. 5 yr. Workers without evidence of lung disease (Group A) had normal PA levels (97.9 .+-. 36.8 versus normal: 102.3 .+-. 10.5 U/mg alb-24 h, p > 0.20), whereas workers with signs of early lung disease as defined by abnormal 67Ga lung scan and rigid pressure-volume curves (Group B) had markedly increased BAL PA activity (477.0 .+-. 171.0 versus 102.3 .+-. 10.5 U/mg alb-24 h, p < 0.01). In contrast, workers with definite asbestosis, as defined by abnormal chest roentgenogram, chest rates, and restrictive pulmonary function tests (Group C), had lower BAL PA levels than workers with early asbestos-induced lung disease (Group B: 477 .+-. 171.0 versus Group C: 120.1 .+-. 20.7, p < 0.05). We conclude that early asbestos-induced alveolitis is asociated with increased lung PA activity, whereas PA activity is normal in the more advanced forms of asbestosis.