Inflammatory and fibrotic mediator release by alveolar macrophages from coal miners

Douglas C. Kuhn, John L. Stauffer, Lesley J. Gaydos, Laurence M. Demers

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6 Scopus citations

Abstract

Eicosanoids and cytokines produced by alveolar macrophages (AM) are key mediators of pulmonary Inflammation and fibrosis. In order to determine if eicosanoid production and cytokine production are altered in AM obtained from coal miners, we compared production of prostaglandin E2(PCE2), thromboxane A2(TXA2), leukotriene B4(LTB4), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα) by cultured AM from normal human subjects and coal miners. The recovery of AM from miners’ lungs by bronchoalveolar lavage was significantly greater than (hat from control subjects. Mean eicosanoid and cytokine production by AM from active miners was also increased compared to AM from control subjects, but this increase was not statistically significant. AM from control subjects produced significantly more TXA2and TNFα when exposed to lipopolysaccharide than did AM from miners. The cyclooxygenase inhibitor suprofen reduced PCE2and TXA2production and TNFα release but had no effect on LTB4production or IL-1β release by miners’ AM. The lipoxygenase inhibitor nordihydroguaiaretic acid attenuated TNFα release, as well as that of LTB4, but had no effect on IL-1β release. Inhibition of thromboxane synthase by UK 38,485 also reduced TNFα release by active miners’ AM but had no effect on PGE2, LTBα production, or IL-1β release. The results of these studies suggest that occupational inhalation of coal dust may increase total lung eicosanoid and cytokine levels and reduce the reactivity of AM to bacterial endotoxin. Furthermore, coal dust-induced changes in both eicosanoid and cytokine release may be subject to pharmacological modulation.

Original languageEnglish (US)
Pages (from-to)9-21
Number of pages13
JournalJournal of Toxicology and Environmental Health
Volume46
Issue number1
DOIs
Publication statusPublished - Sep 1995

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All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pollution

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