Nitric Oxide Production in the Lung and Liver following Inhalation of the Pulmonary Irritant Ozone

  • Jeffrey D. Laskin
  • Diane E. Heck
  • Debra L. Laskin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


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).


Nitric Oxide Alveolar Macrophage Nitric Oxide Production Ozone Exposure Lung Macrophage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations used


alveolar macrophages


interstitial macrophages






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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Jeffrey D. Laskin
    • 1
    • 2
  • Diane E. Heck
    • 1
    • 2
  • Debra L. Laskin
    • 1
    • 2
  1. 1.Environmental and Occupational Health Sciences InstituteRutgers UniversityPiscatawayUSA
  2. 2.Dentistry of New Jersey-Robert Wood Johnson Medical SchoolThe University of MedicinePiscatawayUSA

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