Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1999 May 20

PMID 10330441

Citations 46

Authors

G T De Sanctis

J A MacLean

K Hamada

S Mehta

J A Scott

A Jiao

C N Yandava

L Kobzik

W W Wolyniec

A J Fabian

C S Venugopal

H Grasemann

P L Huang

J M Drazen

Affiliations

Soon will be listed here.

Abstract

Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.

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References

Yates D, Kharitonov S, Thomas P, Barnes P . Endogenous nitric oxide is decreased in asthmatic patients by an inhibitor of inducible nitric oxide synthase. Am J Respir Crit Care Med. 1996; 154(1):247-50. DOI: 10.1164/ajrccm.154.1.8680689. View

MacLean J, Sauty A, Luster A, Drazen J, De Sanctis G . Antigen-induced airway hyperresponsiveness, pulmonary eosinophilia, and chemokine expression in B cell-deficient mice. Am J Respir Cell Mol Biol. 1999; 20(3):379-87. DOI: 10.1165/ajrcmb.20.3.3291. View

Krinzman S, De Sanctis G, Cernadas M, Kobzik L, Listman J, Christiani D . T cell activation in a murine model of asthma. Am J Physiol. 1996; 271(3 Pt 1):L476-83. DOI: 10.1152/ajplung.1996.271.3.L476. View

Lundberg J . Airborne nitric oxide: inflammatory marker and aerocrine messenger in man. Acta Physiol Scand Suppl. 1996; 633:1-27. View

Barnes K, Neely J, Duffy D, Freidhoff L, Breazeale D, Schou C . Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics. 1996; 37(1):41-50. DOI: 10.1006/geno.1996.0518. View

Lambert L, Berling J, Kudlacz E . Characterization of the antigen-presenting cell and T cell requirements for induction of pulmonary eosinophilia in a murine model of asthma. Clin Immunol Immunopathol. 1996; 81(3):307-11. DOI: 10.1006/clin.1996.0194. View

Son H, Hawkins R, Martin K, Kiebler M, Huang P, Fishman M . Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell. 1996; 87(6):1015-23. DOI: 10.1016/s0092-8674(00)81796-1. View

Krinzman S, De Sanctis G, Cernadas M, Mark D, Wang Y, Listman J . Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. J Clin Invest. 1996; 98(12):2693-9. PMC: 507732. DOI: 10.1172/JCI119093. View

Massaro A, Mehta S, Lilly C, Kobzik L, Reilly J, Drazen J . Elevated nitric oxide concentrations in isolated lower airway gas of asthmatic subjects. Am J Respir Crit Care Med. 1996; 153(5):1510-4. DOI: 10.1164/ajrccm.153.5.8630594. View

10.

Roger N, Barbera J, Farre R, Cobos A, Roca J, Rodriguez-Roisin R . Effect of nitric oxide inhalation on respiratory system resistance in chronic obstructive pulmonary disease. Eur Respir J. 1996; 9(2):190-5. DOI: 10.1183/09031936.96.09020190. View

11.

Vaali K, Li L, Redemann B, Paakkari I, Vapaatalo H . In-vitro bronchorelaxing effects of novel nitric oxide donors GEA 3268 and GEA 5145 in guinea-pigs and rats. J Pharm Pharmacol. 1996; 48(12):1309-14. DOI: 10.1111/j.2042-7158.1996.tb03941.x. View

12.

Hogan S, Mould A, Kikutani H, Ramsay A, Foster P . Aeroallergen-induced eosinophilic inflammation, lung damage, and airways hyperreactivity in mice can occur independently of IL-4 and allergen-specific immunoglobulins. J Clin Invest. 1997; 99(6):1329-39. PMC: 507949. DOI: 10.1172/JCI119292. View

13.

. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nat Genet. 1997; 15(4):389-92. DOI: 10.1038/ng0497-389. View

14.

De Sanctis G, Itoh A, Green F, Qin S, Kimura T, Grobholz J . T-lymphocytes regulate genetically determined airway hyperresponsiveness in mice. Nat Med. 1997; 3(4):460-2. DOI: 10.1038/nm0497-460. View

15.

Watkins D, Peroni D, Basclain K, Garlepp M, Thompson P . Expression and activity of nitric oxide synthases in human airway epithelium. Am J Respir Cell Mol Biol. 1997; 16(6):629-39. DOI: 10.1165/ajrcmb.16.6.9191464. View

16.

Renzi P, Sebastiao N, al Assaad A, Giaid A, Hamid Q . Inducible nitric oxide synthase mRNA and immunoreactivity in the lungs of rats eight hours after antigen challenge. Am J Respir Cell Mol Biol. 1997; 17(1):36-40. DOI: 10.1165/ajrcmb.17.1.2307. View

17.

Liu S, Haddad E, Adcock I, Salmon M, Koto H, Gilbey T . Inducible nitric oxide synthase after sensitization and allergen challenge of Brown Norway rat lung. Br J Pharmacol. 1997; 121(7):1241-6. PMC: 1564812. DOI: 10.1038/sj.bjp.0701242. View

18.

De Sanctis G, Wolyniec W, Green F, Qin S, Jiao A, Finn P . Reduction of allergic airway responses in P-selectin-deficient mice. J Appl Physiol (1985). 1997; 83(3):681-7. DOI: 10.1152/jappl.1997.83.3.681. View

19.

Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen G, Irvin C . Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med. 1997; 156(3 Pt 1):766-75. DOI: 10.1164/ajrccm.156.3.9606031. View

20.

Baraldi E, Azzolin N, Zanconato S, Dario C, Zacchello F . Corticosteroids decrease exhaled nitric oxide in children with acute asthma. J Pediatr. 1997; 131(3):381-5. DOI: 10.1016/s0022-3476(97)80062-5. View