CJ Punjabi, JD Laskin, KJ Pendino, NL Goller, SK Durham and DL Laskin
Department of Pharmacology, Rutgers University, Piscataway, NJ 08855- 0789.

Nitric oxide is a highly reactive molecule that has been implicated in host defense and tissue injury. In the present studies, we determined whether rat type II alveolar epithelial cells have the capacity to produce this mediator. We found that type II cells synthesize significant quantities of nitric oxide after treatment with the inflammatory cytokines, interferon-gamma (IFN-gamma) and/or interleukin- 1 beta (IL-1 beta), or with the combination of IFN-gamma and tumor necrosis factor-alpha. In contrast to rat alveolar macrophages, type II cells were unresponsive to lipopolysaccharide. Production of nitric oxide by type II cells in response to IFN-gamma was dose dependent, reaching a maximum at 100 U/ml, and blocked by NG-monomethyl-L-arginine (L-NMA), a nitric oxide synthase inhibitor. Northern blot analysis demonstrated that nitric oxide production by type II cells was due to expression of mRNA for an inducible form of nitric oxide synthase (iNOS). Following brief exposure of rats to irritant-inducing doses of ozone (2 ppm, 3 h), type II cells were found to produce significantly more nitric oxide than were cells from control animals. This was due to increased expression of iNOS mRNA. Cells from ozone-treated rats were also sensitized to produce more nitric oxide in response to IFN-gamma and IL-1 beta. This was associated with a marked increase in expression of iNOS mRNA and enzyme protein in the cells. We also found that ozone inhalation caused enhanced production of hydrogen peroxide, as well as spontaneous and IFN-gamma-induced cytostasis of type II cells toward P815 mouse mastocytoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				W. Song and S. Matalon Modulation of alveolar fluid clearance by reactive oxygen-nitrogen intermediates Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L855 - L858. [Full Text] [PDF]

				W. J. Piotrowski, A. Antczak, J. Marczak, A. Nawrocka, Z. Kurmanowska, and P. Gorski Eicosanoids in Exhaled Breath Condensate and BAL Fluid of Patients With Sarcoidosis Chest, August 1, 2007; 132(2): 589 - 596. [Abstract] [Full Text] [PDF]

				L. Fakhrzadeh, J. D. Laskin, and D. L. Laskin Ozone-induced production of nitric oxide and TNF-{alpha} and tissue injury are dependent on NF-{kappa}B p50 Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L279 - L285. [Abstract] [Full Text] [PDF]

				S. Matalon, K. M. Hardiman, L. Jain, D. C. Eaton, M. Kotlikoff, J. P. Eu, J. Sun, G. Meissner, and J. S. Stamler Regulation of ion channel structure and function by reactive oxygen-nitrogen species Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1184 - L1189. [Abstract] [Full Text] [PDF]

				P. Maestrelli, C. Paska, M. Saetta, G. Turato, Y. Nowicki, S. Monti, B. Formichi, M. Miniati, and L.M. Fabbri Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients Eur. Respir. J., June 1, 2003; 21(6): 971 - 976. [Abstract] [Full Text] [PDF]

				Z. Bebok, K. Varga, J. K. Hicks, C. J. Venglarik, T. Kovacs, L. Chen, K. M. Hardiman, J. F. Collawn, E. J. Sorscher, and S. Matalon Reactive Oxygen Nitrogen Species Decrease Cystic Fibrosis Transmembrane Conductance Regulator Expression and cAMP-mediated Cl- Secretion in Airway Epithelia J. Biol. Chem., November 1, 2002; 277(45): 43041 - 43049. [Abstract] [Full Text] [PDF]

				D.V. Pechkovsky, G. Zissel, C. Stamme, T. Goldmann, H. Ari Jaffe, M. Einhaus, C. Taube, H. Magnussen, M. Schlaak, and J. Muller-Quernheim Human alveolar epithelial cells induce nitric oxide synthase-2 expression in alveolar macrophages Eur. Respir. J., April 1, 2002; 19(4): 672 - 683. [Abstract] [Full Text] [PDF]

				L. Fakhrzadeh, J. D. Laskin, and D. L. Laskin Deficiency in Inducible Nitric Oxide Synthase Protects Mice from Ozone-Induced Lung Inflammation and Tissue Injury Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 413 - 419. [Abstract] [Full Text] [PDF]

				D. Nyhan, S. Kim, S. Dunbar, D. Li, A. Shoukas, and D. E. Berkowitz Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide J Appl Physiol, January 1, 2002; 92(1): 33 - 40. [Abstract] [Full Text] [PDF]

				K. M. Hardiman, J. R. Lindsey, and S. Matalon Lack of amiloride-sensitive transport across alveolar and respiratory epithelium of iNOS({-}/{-}) mice in vivo Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L722 - L731. [Abstract] [Full Text] [PDF]

				H. Kobayashi, R. Hataishi, H. Mitsufuji, M. Tanaka, M. Jacobson, T. Tomita, W. M. Zapol, and R. C. Jones Antiinflammatory Properties of Inducible Nitric Oxide Synthase in Acute Hyperoxic Lung Injury Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 390 - 397. [Abstract] [Full Text]

				S. R. Kleeberger, S. P. M. Reddy, L.-Y. Zhang, H.-Y. Cho, and A. E. Jedlicka Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L326 - L333. [Abstract] [Full Text] [PDF]

				S. Zhu, K. F. Basiouny, J. P. Crow, and S. Matalon Carbon dioxide enhances nitration of surfactant protein A by activated alveolar macrophages Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L1025 - L1031. [Abstract] [Full Text] [PDF]

				J. A. NIGHTINGALE, D. F. ROGERS, K. FAN CHUNG, and P. J. BARNES No Effect of Inhaled Budesonide on the Response to Inhaled Ozone in Normal Subjects Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 479 - 486. [Abstract] [Full Text]

				J. A Nightingale, D. F Rogers, and P. J Barnes Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects Thorax, December 1, 1999; 54(12): 1061 - 1069. [Abstract] [Full Text]

				Y. Bergeron, N. Ouellet, M. Simard, M. Olivier, and M. G. Bergeron Immunomodulation of Pneumococcal Pulmonary Infection with NG-Monomethyl-L-Arginine Antimicrob. Agents Chemother., September 1, 1999; 43(9): 2283 - 2290. [Abstract] [Full Text]

				E. Cadogan, N. Hopkins, S. Giles, J. G. Bannigan, J. Moynihan, and P. McLoughlin Enhanced expression of inducible nitric oxide synthase without vasodilator effect in chronically infected lungs Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L616 - L627. [Abstract] [Full Text] [PDF]

				T. Jilling, I. Y. Haddad, S. H. Cheng, and S. Matalon Nitric oxide inhibits heterologous CFTR expression in polarized epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L89 - L96. [Abstract] [Full Text] [PDF]

				W. S. Cruz, J. A. Corbett, W. J. Longmore, and M. A. Moxley Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L263 - L268. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				S. Zhu, D. L. Kachel, W. J. Martin II, and S. Matalon Nitrated SP-A does not enhance adherence of Pneumocystis carinii to alveolar macrophages Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1031 - L1039. [Abstract] [Full Text] [PDF]

				B. WEINBERGER, L. FAKHRZADEH, D. E. HECK, J. D. LASKIN, C. R. GARDNER, and D. L. LASKIN Inhaled Nitric Oxide Primes Lung Macrophages to Produce Reactive Oxygen and Nitrogen Intermediates Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 931 - 938. [Abstract] [Full Text] [PDF]

				D. C. Thompson, S. E. Porter, A. K. Bauer, K. C. Das, B. Ou, L. Dwyer-Nield, C. W. White, and A. M. Malkinson Cytokine-induced nitric oxide formation in normal but not in neoplastic murine lung epithelial cell lines Am J Physiol Lung Cell Mol Physiol, June 1, 1998; 274(6): L922 - L932. [Abstract] [Full Text] [PDF]

				X. Y. LI, K. DONALDSON, and W. MACNEE Lipopolysaccharide-induced Alveolar Epithelial Permeability . The Role of Nitric Oxide Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): 1027 - 1033. [Abstract] [Full Text] [PDF]

				Y. Bergeron, N. Ouellet, A.-M. Deslauriers, M. Simard, M. Olivier, and M. G. Bergeron Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice Infect. Immun., March 1, 1998; 66(3): 912 - 922. [Abstract] [Full Text] [PDF]

				Y. Guo, M. D. Duvall, J. P. Crow, and S. Matalon Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers Am J Physiol Lung Cell Mol Physiol, March 1, 1998; 274(3): L369 - L377. [Abstract] [Full Text] [PDF]

				J. W. Ding, J. Dickie, H. O'Brodovich, Y. Shintani, B. Rafii, D. Hackam, Y. Marunaka, and O. D. Rotstein Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide Am J Physiol Lung Cell Mol Physiol, March 1, 1998; 274(3): L378 - L387. [Abstract] [Full Text] [PDF]

				D. O'Donnell, J Moynihan, G. Finlay, V. Keatings, C. O'Connor, P McLoughlin, and M. Fitzgerald Exhaled nitric oxide and bronchoalveolar lavage nitrite/nitrate in active pulmonary sarcoidosis Am. J. Respir. Crit. Care Med., December 1, 1997; 156(6): 1892 - 1896. [Abstract] [Full Text]

				L. J. Janssen, I. McGrogan, J. Wattie, P. M. O'Byrne, and E. E. Daniel Myogenic and neurogenic mechanisms and arachidonate metabolites in bronchial muscle response to allergen Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1118 - L1125. [Abstract] [Full Text] [PDF]

				T. C. Brady, L.-Y. Chang, B. J. Day, and J. D. Crapo Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-kappa B activation Am J Physiol Lung Cell Mol Physiol, November 1, 1997; 273(5): L1002 - L1006. [Abstract] [Full Text] [PDF]

				R. J. Folz, J. Guan, M. F. Seldin, T. D. Oury, J. J. Enghild, and J. D. Crapo Mouse Extracellular Superoxide Dismutase: Primary Structure, Tissue-specific Gene Expression, Chromosomal Localization, and Lung In Situ Hybridization Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 393 - 403. [Abstract] [Full Text]

				P. Juvin, T. Fournier, M. Grandsaigne, J.-M. Desmonts, and M. Aubier Diesel particles increase phosphatidylcholine release through a NO pathway in alveolar type II cells Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L1075 - L1081. [Abstract] [Full Text] [PDF]

				V. R. Sunil, A. J. Connor, Y. Guo, J. D. Laskin, and D. L. Laskin Activation of type II alveolar epithelial cells during acute endotoxemia Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L872 - L880. [Abstract] [Full Text] [PDF]

				D. V. Pechkovsky, G. Zissel, T. Goldmann, M. Einhaus, C. Taube, H. Magnussen, M. Schlaak, and J. Muller-Quernheim Pattern of NOS2 and NOS3 mRNA expression in human A549 cells and primary cultured AEC II Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L684 - L692. [Abstract] [Full Text] [PDF]