Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 931-938

Inhaled Nitric Oxide Primes Lung Macrophages to Produce Reactive Oxygen and Nitrogen Intermediates

BARRY WEINBERGER, LADAN FAKHRZADEH, DIANE E. HECK, JEFFREY D. LASKIN, CAROL R. GARDNER, and DEBRA L. LASKIN

Division of Neonatology, Department of Pediatrics and the Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Rutgers University, Piscataway, New Jersey

Inhaled nitric oxide is a selective pulmonary vasodilator used for the treatment of pulmonary hypertension. The potential adverse effects of inhaled nitric oxide are unknown and represent the focus of the present studies. Whereas inhalation of nitric oxide (10 to 100 ppm, 5 h) by Balb/c mice had no effect on the number or type of cells recovered from the lung, a dose-related increase in bronchoalveolar lavage protein was observed, suggesting that nitric oxide induces alveolar epithelial injury. To determine if this was associated with altered alveolar macrophage activity, we quantified production of reactive oxygen and nitrogen intermediates by these cells. Interferon-, alone or in combination with lipopolysaccharide (LPS), induced expression of inducible nitric oxide synthase (iNOS) protein and nitric oxide production by alveolar macrophages. Cells from mice exposed to 20 to 100 ppm nitric oxide produced significantly more nitric oxide and expressed greater quantities of iNOS than cells from control animals. Superoxide anion production and peroxynitrite generation by alveolar macrophages were also increased after exposure of mice to nitric oxide. This was correlated with increased antinitrotyrosine antibody binding to macrophages in histologic sections. Taken together, these data demonstrate that inhaled nitric oxide primes lung macrophages to release reactive oxygen and nitrogen intermediates. Increased production of these mediators by macrophages following inhalation of nitric oxide may contribute to tissue injury.

This article has been cited by other articles:

				T.-M. Yu, Y.-H. Chen, J.-Y. Hsu, C.-S. Sun, Y.-W. Chuang, C.-H. Chen, M.-J. Wu, C.-H. Cheng, and K.-H. Shu Systemic inflammation is associated with pulmonary hypertension in patients undergoing haemodialysis Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1946 - 1951. [Abstract] [Full Text] [PDF]

				J. B. Mannick Immunoregulatory and antimicrobial effects of nitrogen oxides. Proceedings of the ATS, January 1, 2006; 3(2): 161 - 165. [Abstract] [Full Text] [PDF]

				X. Peng, R.-E. E. Abdulnour, S. Sammani, S.-F. Ma, E. J. Han, E. J. Hasan, R. Tuder, J. G. N. Garcia, and P. M. Hassoun Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 470 - 479. [Abstract] [Full Text] [PDF]

				J. D. Lang, M. Figueroa, K. D. Sanders, M. Aslan, Y. Liu, P. Chumley, and B. A. Freeman Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury Am. J. Respir. Crit. Care Med., January 15, 2005; 171(2): 147 - 157. [Abstract] [Full Text] [PDF]

				K. Nagata, Y. Iwasaki, Y. Takemura, H. Harada, I. Yokomura, S. Fushiki, and M. Nakagawa Effect of Inhaled NG-Nitro-L-Arginine Methyl Ester on Candida-Induced Acute Lung Injury Chest, December 1, 2003; 124(6): 2293 - 2301. [Abstract] [Full Text] [PDF]

				S. M. Lowson Nitric Oxide Signaling and Clinical Alternatives to Nitric Oxide Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 239 - 252. [Abstract] [PDF]

				D. E. Heck, A. M. Vetrano, T. M. Mariano, and J. D. Laskin UVB Light Stimulates Production of Reactive Oxygen Species: UNEXPECTED ROLE FOR CATALASE J. Biol. Chem., June 13, 2003; 278(25): 22432 - 22436. [Abstract] [Full Text] [PDF]

				A. R. Glanville Inhaled Nitric Oxide after Lung Transplantation: No More Cosmesis? Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1463 - 1464. [Full Text] [PDF]

				M. C. Walters, A. W. Nienhuis, and E. Vichinsky Novel Therapeutic Approaches in Sickle Cell Disease Hematology, January 1, 2002; 2002(1): 10 - 34. [Abstract] [Full Text]

				K. Stuart-Smith and J. Y. Jeremy Microvessel damage in acute respiratory distress syndrome: the answer may not be NO Br. J. Anaesth., August 1, 2001; 87(2): 272 - 279. [Abstract] [Full Text] [PDF]

				B. Weinberger, D. L. Laskin, D. E. Heck, and J. D. Laskin The Toxicology of Inhaled Nitric Oxide Toxicol. Sci., January 1, 2001; 59(1): 5 - 16. [Abstract] [Full Text] [PDF]

				E. R. Schmid, C. Burki, M. H. C. Engel, D. Schmidlin, M. Tornic, and B. Seifert Inhaled Nitric Oxide Versus Intravenous Vasodilators in Severe Pulmonary Hypertension After Cardiac Surgery Anesth. Analg., November 1, 1999; 89(5): 1108 - 1108. [Abstract] [Full Text] [PDF]