Influence of mineral dusts on metabolism of arachidonic acid by alveolar macrophage.
The alveolar macrophage (AM) responds to stimuli such as coal mine dust by releasing inflammatory mediators such as cytokines, growth factors, reactive oxygen species, and eicosanoids. Eicosanoids are synthesized by AM through the action of cyclooxygenase and lipoxygenase enzymes and serve to modulate the proinflammatory function of this cell as part of the lungs' host defense mechanism. Reactive oxygen species can be generated by AM as a by-product in the biosynthetic pathway of the prostaglandins. AM produces primarily prostaglandin E2, thromboxane A2, and leukotriene B4 as part of the cellular response to an inflammatory stimulus. There is evidence to suggest that eicosanoid production by AM is functionally linked to both surface interaction with mine dust particles like silica and by the phagocytosis of the dust particle itself. In this report, we examined the effects of an antioxidant, vitamin E, on dust-induced synthesis of PGE2 and TXB2 in vitro and in vivo by AM obtained by bronchoalveolar lavage from rats. We also looked at the effects of the surface of silica particles on AM eicosanoid biosynthesis under conditions of calcination, a process that removes exposed hydroxyl groups from the surface of silica particles, thus reducing the likelihood of soluble hydroxyl radical formation. Treatment of AM with vitamin E in vivo and in vitro reduced the augmentation in eicosanoid production usually observed when AM are exposed to mine dusts. These results suggest that vitamin E may effectively reduce the inflammatory and fibrotic response produced by inhalation of mineral dust through an antioxidant mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Demers
L M
LM
Department of Pathology, M.S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Kuhn
D C
DC
D016718:Arachidonic Acid / Q000378:metabolism*; D004391:Dust / Q000009:adverse effects*; D015777:Eicosanoids / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008903:Minerals / Q000009:adverse effects*; D012822:Silicon Dioxide / Q000494:pharmacology; D013499:Surface Properties
D004391:Dust; D015777:Eicosanoids; D018836:Inflammation Mediators; D008903:Minerals; D016718:Arachidonic Acid; D012822:Silicon Dioxide