Inflammatory and fibrotic mediator release by alveolar macrophages from coal miners.
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 (PGE2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) by cultured AM from normal human subjects and coal miners. The recovery of AM from miners' lungs by bronchoalveolar lavage was significantly greater than that 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 TXA2 and TNF alpha when exposed to lipopolysaccharide than did AM from miners. The cyclooxygenase inhibitor suprofen reduced PGF2 and TXA2 production and TNF alpha release but had no effect on LTB4 production of IL-1 beta release by miners' AM. The lipoxygenase inhibitor nordihydroguaiaretic acid attenuated TNF alpha release, as well as that of LTB4, but had no effect on IL-1 beta release. Inhibition of thromboxane synthase by UK 38,485 also reduced TNF alpha release by active miners' AM but had no effect on PGE2, LTB4 production, or IL-1 beta 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.
Kuhn
D C
DC
Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Stauffer
J L
JL
Gaydos
L J
LJ
Demers
L M
LM
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D003032:Coal Mining; D016207:Cytokines / Q000378:metabolism*; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005355:Fibrosis / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D016273:Occupational Exposure
D016207:Cytokines; D015777:Eicosanoids; D008070:Lipopolysaccharides