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 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)
Garcia
J G
JG
Department of Internal Medicine, Indiana University School of Medicine, Indianapolis 46202.
Griffith
D E
DE
Cohen
A B
AB
Callahan
K S
KS
D000328:Adult; D001194:Asbestos / Q000009:adverse effects*; D001195:Asbestosis / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology; D004781:Environmental Exposure; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology*; D012123:Pulmonary Ventilation; D012907:Smoking / Q000378:metabolism; D014109:Total Lung Capacity
D001194:Asbestos; D007975:Leukotriene B4