Nitric Oxide Production in the Lung and Liver following Inhalation of the Pulmonary Irritant Ozone
Following irritation or injury, an array of growth factors and cytokines as well as lipid mediators accumulate in target tissues. It is becoming increasingly apparent that many of these agents can cause both immune and nonimmune cells within the tissue to secrete nitric oxide (Nathan, 1992; Laskin et al., 1994). Nitric oxide is a highly reactive mediator that plays a critical role in a variety of physiological processes including non-specific host defense (Nathan 1992). Nitric oxide also regulates vascular tone, gastric motility, neurotransmission (Moncada et al., 1991; Nathan, 1992), bone marrow cell growth and development (Punjabi et al., 1992, 1994b) as well as wound healing (Heck, et al., 1992). Nitric oxide is generated enzymatically in mammalian cells by the NADPH-dependent enzyme, nitric oxide synthase, from the amino acid 1-arginine (Nathan 1992; Nathan and Xie, 1994). Enzyme activity requires flavin mononucleotide, adenine dinucleotide, tetrahydrobiopterin and in some cases, calcium and calmodulin as cofactors. Three different isoforms of nitric oxide synthase have been characterized including two constitutively expressed, relatively low output forms of the enzyme, and one relatively high output cytokine-inducible form of the enzyme (Nathan and Xie, 1994). Constitutive forms of nitric oxide synthase have been identified in endothelial cells and the brain and are known to require calcium and calmodulin for activity. The cytokine inducible form is not calcium-dependent. Although first characterized in macrophages, this form of the enzyme can be induced in many cell types including endothelial cells, epithelial cells, hepatocytes and neurons (Nathan and Xie, 1994).
KeywordsNitric Oxide Alveolar Macrophage Nitric Oxide Production Ozone Exposure Lung Macrophage
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- 5.Kushmer I, Mackiewicz J. Acute phase proteins as disease markers. Dis Markers 5: 1–15, 1987.Google Scholar
- 7.Laskin, DL, Rodrigues-del Valle, M, Heck, DE, Hwang, SM, Ohnishi, ST, Durham, SK, Goller, NL, Laskin, JD. Hepatic nitric oxide production following acute endotoxemia in rats is mediated by increased inducible nitric oxide synthase gene expression, Hepatology, in press, 1995.Google Scholar
- 8.Lippman M. Health effects of ozone. A critical review. J Air Poll Control Assoc 39: 672–695 (1989).Google Scholar
- 13.Nathan, CF, Xie, QW, Regulation of biosynthesis of nitric oxide. J. Biol. Chem. 268: 13, 725–13, 728, 1994.Google Scholar
- 14.Pendino K, Punjabi C, Lavnikova N, Gardner C, Laskin J, Laskin D. Inhalation of ozone stimulates nitric oxide production by pulmonary alveolar and interstitial macrophages. Am Rev Respir Dis 145: A650, 1992.Google Scholar
- 17.Prokhorova S, Lavnikova N, Laskin DL. Characterization of interstitial macrophages and subpopulations of alveolar macrophages from rat lung. J Leuk Biol, 55: 141–146, 1994.Google Scholar
- 18.Punjabi, CJ, Laskin, DL, Heck, D, Laskin, JD. Nitric oxide production by murine bone marrow cells: Inverse correlation with cellular proliferation. J. Immunology 149: 2179–2184, 1992.Google Scholar
- 20.Punjabi, CJ, Laskin, JD, Hwang, SM, MacEachern, L, Laskin, DL. Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage stimulating factor (GM-CSF) after benzene treatment of mice. Blood 83: 3255–3263, 1994b.PubMedGoogle Scholar