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
asbestos-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
asbestosis (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/10(6) alveolar macrophages for patients with
asbestosis, 1.05 +/- 0.2 ng/10(6) cells in
asbestos workers without
asbestosis, 0.9 +/- 0.2 ng/10(6) cells in control nonsmokers, and 0.2 +/- 0.05 ng/10(6) 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.(ABSTRACT TRUNCATED AT 250 WORDS)