Korean J Physiol Pharmacol.  1998 Apr;2(2):233-239.

Inducible nitric oxide synthase mRNA expression and nitric oxide production in silica-induced acute inflammatory lung injury

• Lee J

Abstract

Stimulated alveolar macrophages and neutrophils produce nitric oxide, a free radical by an inducible nitric oxide synthase (iNOS), which reacts with superoxide anion to form peroxynitrite, a more highly reactive toxic species. The objectives of the present study were to evaluate acute inflammatory lung injury and to determine iNOS mRNA induction and nitric oxide production by rat broncho-alveolar lavage cells following intratracheal treatment of silica. After 4 h exposure to silica, differential counts of bronchoalveolar lavage cells and lactate dehydrogenase (LDH) activity as well as total protein in the broncho-alveolar lavage fluid were determined. Broncho-alveolar lavage cells were also assayed for iNOS mRNA and the productions of nitrite and nitrate measured in the cells cultured. Differential analysis of broncho-alveolar lavage cells showed that the number of alveolar macrophages slightly decreased following silica treatment; however, red blood cells, lymphocytes, and neutrophils significantly were increased by 9-, 14-, and 119-fold following silica treatment, respectively, compared with the saline control. It was also found significant increases in the LDH activity and total protein in the lavage fluid obtained from silica-treated rats, indicating silica-induced acute lung injury. Northern blot analysis demonstrated that the steady state levels of iNOS mRNA in broncho-alveolar lavage cells were increased following silica treatment. The productions of nitrite and nitrate in the cultured cells were significantly increased by 2-fold following silica treatment, respectively, which were attenuated by the NOS inhibitor Nomega-nitro-L-arginine-methyl ester(L-NAME) and partially reversed by L-arginine. These findings suggest that nitric oxide production in alveolar macrophages and recruited neutrophils is increased in response to silica. Nitric oxide may contribute in part to acute inflammatory lung injury.

Keyword

iNOS mRNA; Nitric oxide; Silica; Acute inflammatory lung injury

MeSH Terms

Acute Lung Injury
Animals
Arginine
Blotting, Northern
Bronchoalveolar Lavage
Cells, Cultured
Erythrocytes
L-Lactate Dehydrogenase
Lung Injury*
Lung*
Lymphocytes
Macrophages, Alveolar
Neutrophils
Nitric Oxide Synthase Type II*
Nitric Oxide*
Peroxynitrous Acid
Rats
RNA, Messenger*
Silicon Dioxide
Superoxides
Therapeutic Irrigation
Arginine
L-Lactate Dehydrogenase
Nitric Oxide
Nitric Oxide Synthase Type II
Peroxynitrous Acid
RNA, Messenger
Silicon Dioxide
Superoxides