Effect of in vivo coal dust exposure on arachidonic acid metabolism in the rat alveolar macrophage.
Oxygenated metabolites of arachidonic acid (AA) are produced by the alveolar macrophage (AM) and have been shown to mediate inflammatory reactions. We therefore assessed the production of eicosanoids by AM harvested from the lungs of rats exposed to a bituminous coal dust for 2 wk in an inhalation chamber in order to determine if AA metabolism was altered in a manner that may promote an inflammatory response in the lung. Exposure to coal dust resulted in a 66% increase in the number of AM harvested, an increase in thromboxane A2 (TxA2) and leukotriene B4 (LTB4) production to 222% and 181% of control values, respectively, and a decrease in prostaglandin E2 (PGE2) production to 62% of control values. In AM harvested from rats allowed to breath clean air for 2 wk following coal dust exposure, PGE2 production returned to control levels but TxA2 and LTB4 production remained elevated. The TxA2 synthesis inhibitor UK 38,485 reduced TxA2 production in dust-exposed AM both immediately and 2 wk following exposure. Thus, exposure of rats to coal dust significantly alters the metabolism of AA in AM, with potentially important aspects of AA metabolism remaining altered even after a 2-wk recovery period. Based on the established role of eicosanoids in inflammatory and fibrotic processes, these results suggest that the alteration of AM eicosanoid production as a result of the inhalation of coal mine dust may be an important factor in the pathophysiology of coal workers' pneumoconiosis.
Kuhn
D C
DC
Department of Pathology, Pennsylvania State University, M.S. Hershey Medical Center, Hershey 17033.
Stanley
C F
CF
el-Ayouby
N
N
Demers
L M
LM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003031:Coal; D015232:Dinoprostone / Q000378:metabolism; D004391:Dust; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D007093:Imidazoles / Q000378:metabolism; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D003031:Coal; D004391:Dust; D015777:Eicosanoids; D007093:Imidazoles; D007975:Leukotriene B4; D016718:Arachidonic Acid; C039242:dazmegrel; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D015232:Dinoprostone