Induction of the inducible nitric-oxide synthase gene by intratracheal instillation of silica, coal, titanium-dioxide and carbonyl iron.
Blackford-J; Castranova-V; Jones-W; Dey-R
FASEB J 1995 Mar; 9(3)(I):A131
The effects of various respirable dusts on inducible nitric oxide synthase (iNOS) gene was analyzed to determine if there is a difference in the ability each dust to increase expression of the iNOS gene in alveolar macrophages (AM) and neutrophils. After 24 hours, Northern analysis and a chemiluminescence assay were used to measure changes in iNOS gene expression and NO· production. Rats were intratracheally instilled with 5 mg/100gbw of silica, coal, carbonyl iron and Ti02. The dust particles averaged less than 5 microm in diameter. Each dust increased the levels of AM NO·-dependent chemiluminescence, indicating an increased production of NO·. Silica and Ti02 both increased the levels of iNOS mRNA while iron and coal did not. Each dust caused an increase in neutrophil numbers, indicating an inflammatory response, while only iron and Ti02 increased the numbers of AM. We conclude that particles, both highly toxic and less toxic, triggers iNOS gene expression in AM and neutrophils, but that there is a difference in the capacity of each particle to induce the iNOS gene and therefore the production of NO·. NO· is theorized to contribute to the early inflammatory damage observed in the lung following dust exposure.
Biological-effects; Biological-systems; Cell-biology; Cell-function; Cellular-reactions; Coal-dust; Dust-exposure; Dust-inhalation; Genes; Genetic-factors; Inhalation-studies; Iron-compounds; Laboratory-animals; Laboratory-testing; Lung-function; Lung-irritants; Molecular-biology; Pulmonary-system; Respiratory-irritants
Abstract; Conference/Symposia Proceedings
The FASEB Journal. Experimental Biology 95 - Annual Meeting of Professional Research Scientists, Atlanta, Georgia, April 9-13, 1995