CHARACTERIZATION OF ALVEOLAR MACROPHAGE EICOSANOID PRODUCTION IN A NONHUMAN PRIMATE MODEL OF MINERAL DUST EXPOSURE

The relative activation of eicosanoid production which results from th e exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung diseas e. We compared in vitro basal and silica-stimulated production of pros taglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nomistrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and eva luated AM eicosanoid production at two week intervals following dust i nstillation. Unstimulated AM from humans produce more PGE2 and TXA2 th an do AM from M. nemistrina. However, in vitro exposure of AM from bot h species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequentia l analysis of AM eicosanoid production following a single bolus exposu re to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dus t or crystalline silica showed marked variability among individual non -human primates in qualitative and quantitative aspects of dust-induce d eicosanoid production. However, the rank order of potency of the dif ferent dusts (silica > anthracite > bituminous) correlated with epidem iological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to min eral dust exposure.