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Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma
被引:184
作者:
De Sanctis, GT
MacLean, JA
Hamada, K
Mehta, S
Scott, JA
Jiao, AP
Yandava, CN
Kobzik, L
Wolyniec, WW
Fabian, AJ
Venugopal, CS
Grasemann, H
Huang, PL
Drazen, JM
机构:
[1] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Dept Allergy & Clin Immunol, Cardiac Unit, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA
[6] Univ Western Ontario, London Hlth Sci Ctr, Div Pulm, Dept Med, London, ON N6A 4G5, Canada
[7] Univ Western Ontario, London Hlth Sci Ctr, Dept Pharmacol, London, ON N6A 4G5, Canada
[8] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
[9] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
关键词:
nitric oxide;
allergen;
mice;
asthma;
nitric oxide synthase;
D O I:
10.1084/jem.189.10.1621
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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 signifcantly 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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页码:1621 / 1629
页数:9
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