COMPARISON OF INDUCIBLE NITRIC-OXIDE SYNTHASE GENE-EXPRESSION AND LUNG INFLAMMATION FOLLOWING INTRATRACHEAL INSTILLATION OF SILICA, COAL, CARBONYL IRON, OR TITANIUM-DIOXIDE IN RATS

The pulmonary toxicity oi the respirable dusts silica, coal, carbonyl iron, and titanium dioxide on alveolar macrophage (AM) and neutrophil (PMN) inducible nitric oxide synthase (iNOS) gene expression and nitri c oxide (NO) production was investigated. Rats were intratracheally in stilled with 5 mg/100 g body weight of silica, coal, carbonyl iron, or titanium dioxide. The dust particles averaged less than 5 mu m in dia meter. Bronchoalveolar lavage was performed 24 h later. Bronchoalveola r lavage cell (BALC) differentials, iNOS gene expression and NO produc tion by BALC (measured indirectly as NO-dependent chemiluminescence), and lavageable lung protein levels were measured. Analyzed on an equal mass basis, silica, coal, and titanium dioxide dusts increased the pr oduction oi iNOS-dependent NO by AM. Silica and titanium dioxide both increased the levels of iNOS mRNA while carbonyl iron and coal did not . Each dust caused an increase in PMN, indicating an inflammatory resp onse. Carbonyl iron and titanium dioxide decreased the numbers of AM. Levels of acellular lavageable lung protein were increased by silica, carbonyl iron, and titanium dioxide. When exposure was normalized for an equal number oi particles, the pneumotoxic dusts, silica and coal, caused more inflammation and NO production than the nuisance dusts, ca rbonyl iron and titanium dioxide. Therefore, it appears that particle number is a more appropriate metric oi exposure than mass when compari ng the relative pathogenicity oi dusts oi different sizes. Furthermore , since the potency of these dusts (on a particle number basis) to inc rease iNOS gene expression reflects their inflammatory and pathogenic potential, it is proposed that NO may contribute to the early inflamma tory damage observed in the lung following dust exposure.