Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B₄

The alveolar influx and subsequent activation of inflammatory cells such as neutrophils and eosinophils are believed to be important in the pathogenesis of many interstitial lung disorders, including asbestosis. Indices of lower respiratory tract abnormalities detected by bronchoalveolar lavage (BAL) were investigated in 93 asbestosis-exposed workers as well as in smoking (n = 12) and nonsmoking (n = 10) control subjects. Patients with clinical asbestosis (n = 12) exhibited increases in both BAL neutrophils and BAL eosinophils, expressed as both percentage of total cells and total numbers, when compared to asbestos-exposed workers without asbestos (n = 81) and control subjects. Significantly greater numbers of BAL neutrophils were also found in asbestos-exposed workers without asbestosis than in either smoking or nonsmoking control subjects. These abnormalities correlated significantly with in vitro BAL alveolar macrophage production of the potent leukocyte chemotaxin, leukotriene B₄ (LTB₄). For example, basal, unstimulated LTB₄ production was 3.1 ± 0.8 ng/10⁶ alveolar macrophages for patients with asbestosis, 1.05 ± 0.2 ng/10⁶ cells in asbestos workers without asbestosis, 0.9 ± 0.2 ng/10⁶ cells in control nonsmokers, and 0.2 ± 0.05 ng/10⁶ cells in control smokers. Stimulated LTB₄ release from BAL alveolar macrophages (A23187 or arachidonate) was even more pronounced in asbestos workers with or without asbestosis, suggesting an in vivo priming effect on alveolar macrophage synthesis of LTB₄. Cell-free BAL supernatants from asbestos-exposed patients with or without asbestosis also contained significantly greater amounts of LTB₄ than did those from control subjects, indicating enhanced in vivo production of this inflammatory mediator. Physiologic derangement (such as reduction in total lung capacity and forced vital capacity) and radiographic abnormalities (worsening profusion score) correlated well with the percentage and total numbers of BAL neutrophils and eosinophils. These results suggest that inflammatory cell infiltration into alveolar compartments in response to stimulated alveolar macrophage production of LTB₄ may potentially be important in both inflammatory and fibrotic responses that occur after occupational asbestos exposure.