SUPEROXIDE ANION GENERATION BY ALVEOLAR INFLAMMATORY CELLS IN SIMPLE PNEUMOCONIOSIS AND IN PROGRESSIVE MASSIVE FIBROSIS OF NONSMOKING COAL-WORKERS

We have examined superoxide anion (O2̄) release by alveolar inflammatory cells recovered by bronchoalveolar lavage from the lower respiratory tract of 10 healthy nonsmokers and 25 nonsmoking pneumoconiotic patients, 11 with radiographic changes of simple pneumoconiosis (SP) and 14 with changes of progressive massive fibrosis (PMF). Significant increased number of cells was recovered from the lower respiratory tract from both patients with SP or with PMF. Alveolitis was made up predominantly of alveolar macrophages (AM) and an increased percentage of neutrophils in patients with PMF (3.3 ± 0.7%). O2̄ release was evaluated using a superoxide dismutase (SOD)-inhibitable lucigenin-dependent chemiluminescence method. Spontaneous O2̄ generation by alveolar inflammatory cells from pneumoconiotic patients with SP was three to four times greater than that from 10 age-matched, healthy control subjects. O2̄ release by alveolar inflammatory cells from patients with PMF was dramatically increased when compared with that in patients with SP and with that in control subjects and was observed before and after stimulation by phorbol myristate acetate (PMA) (p < 0.001). The increased O2̄ release was not due to a lack of enzyme antioxidant system within AM since intracellular superoxide dismutase was not lower in AM from patients than in AM from control subjects (p < 0.05). Alteration of DL(CO) correlated with PMA-induced superoxide release by alveolar inflammatory cells in patients with PMF (p < 0.05). Our data demonstrate that alveolar inflammatory cells from pneumoconiotic patients with PMF are in the activated state and release more oxygen-reactive species that do those from patients with SP. In addition, the fact that patients with PMF demonstrated significantly lower values of lung volumes and diffusing capacity than did those with SP support the concept that O2̄ generation by AM may play a role in lung injury in coal workers' pneumoconiosis.