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

Our plain-English summary of Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4, by J.G. Garcia, D.E. Griffith, A.B. Cohen, et al (The American Review of Respiratory Disease, 1989).

The study

• Authors: J.G. Garcia, D.E. Griffith, A.B. Cohen, K.S. Callahan
• Journal: The American Review of Respiratory Disease
• Published: 1989;139(6):1494-501
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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)

In plain English

The authors studied lung washings (bronchoalveolar lavage) from 93 workers with occupational asbestos exposure, 12 with clinical asbestosis and 81 without. They compared them with 10 nonsmoking and 12 smoking control subjects who had no asbestos exposure. Lung cells, mainly alveolar macrophages, were tested for release of leukotriene B4 (LTB4), a substance that attracts inflammatory white cells. Workers with asbestosis had more neutrophils and eosinophils in lavage fluid than the other groups. Exposed workers without asbestosis had more neutrophils than controls. Basal, unstimulated LTB4 release was 3.1 ± 0.8 ng per million macrophages in workers with asbestosis, 1.05 ± 0.2 in exposed workers without asbestosis, 0.9 ± 0.2 in nonsmoking controls and 0.2 ± 0.05 in smoking controls. After stimulation, macrophages from both exposed groups released more LTB4 than those from nonsmoking controls. Most asbestos bodies had amphibole cores, over 90% amosite. Eosinophil counts correlated with lower lung function and worse chest X-ray scores. The authors concluded that LTB4 from alveolar macrophages may be an important mechanism by which lung inflammation is amplified after asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective clinical study comparing bronchoalveolar lavage (BAL) findings, with laboratory testing of the recovered lung cells, in asbestos-exposed workers and control subjects
• Who was studied: 93 consecutive patients with occupational asbestos exposure: 12 with clinical asbestosis (Group I) and 81 without asbestosis (Group II). Controls were 10 normal nonsmoking volunteers aged 24 to 44 (Group III) and 12 current smokers aged 51 to 68 without asbestos exposure who had mild to moderate obstructive lung disease (Group IV). The article does not state where or when the patients were studied.
• Exposure: Occupational asbestos exposure, averaging 20.2 ± 2.9 years in the asbestosis group and 23.5 ± 1.0 years in exposed workers without asbestosis. Electron microscopy found that most ferruginous (asbestos) bodies in lavage fluid had amphibole cores, more than 90% amosite. Crocidolite and tremolite were not identified. Chrysotile made up less than 10% of the uncoated fiber load.
• Main results:
  • Workers with asbestosis had more BAL neutrophils and eosinophils than exposed workers without asbestosis and than controls. Neutrophils were 8.0 ± 4.2% of lavage cells in the asbestosis group versus 3.1 ± 0.4% in exposed workers without asbestosis (p = 0.01).
  • Exposed workers without asbestosis (Group II) had significantly more BAL neutrophils than nonsmoking controls (Group III), p = 0.04.
  • Basal, unstimulated LTB4 release by alveolar macrophages was 3.1 ± 0.8 ng per million macrophages in workers with asbestosis, 1.05 ± 0.2 in exposed workers without asbestosis, 0.9 ± 0.2 in control nonsmokers and 0.2 ± 0.05 in control smokers.
  • Basal LTB4 release in the asbestosis group was significantly greater than in exposed workers without asbestosis (the p-value is illegible in the scanned text) and than in nonsmoking controls (p = 0.05).
  • After stimulation with A23187 or arachidonate, macrophages from workers with asbestosis released significantly more LTB4 than those from nonsmoking controls (p = 0.02 for both).
  • Macrophages from exposed workers without asbestosis also released more LTB4 than those from nonsmoking controls after ionophore (p = 0.01) or arachidonate (p = 0.001) stimulation.
  • In a limited number of cell-free lavage fluid samples, both exposed groups (with and without asbestosis) had significantly more LTB4 than control subjects.
  • Nonsmoking exposed workers without asbestosis (n = 21) were compared with nonsmoking controls (n = 10). Basal LTB4 release was comparable, but their stimulated LTB4 release was significantly greater (p = 0.006 ionophore, p = 0.01 arachidonate), and they had more BAL neutrophils (p = 0.05).
  • Workers with asbestosis had significantly more ferruginous bodies in lavage fluid than exposed workers without asbestosis. None were detected in nonsmoking controls.
  • In exposed workers, total BAL eosinophils were inversely related to forced vital capacity (r = -0.22, p = 0.01) and total lung capacity (r = -0.31, p = 0.001). They were directly correlated with worsening chest X-ray profusion score (r = 0.54, p = 0.001).
  • No significant correlation was found between smoking and BAL neutrophils, eosinophils, asbestos bodies or LTB4 values.
• The authors' conclusion: The authors concluded that production of LTB4 by alveolar macrophages may be an important mechanism by which lung inflammation is amplified after asbestos exposure in humans. They also suggested that macrophages from asbestos-exposed workers appear primed to release LTB4.
• Limitations the authors state:
  • The authors stated that the mechanism behind the apparent priming of macrophage LTB4 production is unclear. Their explanation, activation by asbestos fibers and/or other substances in the body rather than smoking, was not specifically tested in this study.
  • Cigarette smoking was frequently present in the study population and was a potential source of cell activation.
  • Ages differed between the study groups.
  • Only basal LTB4 values were available for the smoking control group.
  • LTB4 in cell-free lavage fluid was measured in only a limited number of samples.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Asbestos Exposure, Interstitial, Bronchoalveolar Lavage (BAL).

Related studies

• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization — K. Donaldson, X.Y. Li, et al. (1992)
• Effects of asbestos and beryllium on release of alveolar macrophage enzymes — K.Y. Kang, D. Bice, et al. (1979)
• Asbestos stimulates alveolar macrophages to release a factor causing human lung fibroblasts to replicate — P. Bitterman, S. Rennard, et al. (1981)
• Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis — W.N. Rom, T. Harkin (1991)

Browse more research in The American Review of Respiratory Disease, or return to medical research.