Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure.
The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nemestrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE2 and TXA2 than do AM from M. nemestrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological 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 mineral dust exposure.
Kuhn
D C
DC
Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Griffith
J W
JW
Stauffer
J L
JL
Riling
S
S
Demers
L M
LM
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003031:Coal / Q000633:toxicity; D015232:Dinoprostone / Q000096:biosynthesis; D004391:Dust; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007700:Kinetics; D008254:Macaca nemestrina; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000633:toxicity*; D016273:Occupational Exposure; D011791:Quartz; D012822:Silicon Dioxide / Q000633:toxicity; D013929:Thromboxane B2 / Q000096:biosynthesis; D014025:Titanium / Q000633:toxicity
D003031:Coal; D004391:Dust; D015777:Eicosanoids; D008903:Minerals; D011791:Quartz; C009495:titanium dioxide; D013929:Thromboxane B2; D012822:Silicon Dioxide; D014025:Titanium; D015232:Dinoprostone