The effect of overexpression of endothelial nitric oxide synthase on eosinophilic lung inflammation in a murine model.
The effects of nitric oxide (NO) on allergic inflammation are controversial. In particular, the role of endothelial nitric oxide synthase (eNOS) in asthma remains uncertain. In the present study, we examined the effects of overexpression of eNOS on allergic inflammation using eNOS transgenic (eNOS-Tg) mice, in which eNOS protein is overexpressed in the vascular endothelium and airway epithelium. We found that eNOS-Tg mice showed a reduction of the asthmatic response to allergen challenge. Eosinophilic accumulation in the airspaces, eosinophilic activity, and bronchial responsiveness to acetylcholine were significantly attenuated in eNOS-Tg mice, as compared with wild-type mice following ovalbumin sensitization/challenge, even though the levels of circulating eosinophils were comparable in the wild-type and eNOS-Tg mice. The concentrations of eotaxin in the bronchoalveolar lavage fluid were significantly less in eNOS-Tg mice than in the wild-type mice. In addition, immunohistochemical analysis showed that the expressions of both intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on the pulmonary endothelium of eNOS-Tg mice was decreased compared with the controls. These results suggest that chronic eNOS overexpression contributes to the suppression of allergic inflammation by reducing the production of eotaxin in the airspaces and/or the expression of adhesion molecules in the vascular endothelium.
Kobayashi
Kazuyuki
K
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Nishimura
Yoshihiro
Y
Yamashita
Tomoya
T
Nishiuma
Teruaki
T
Satouchi
Miyako
M
Yokoyama
Mitsuhiro
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047209:Eosinophil Peroxidase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D004791:Enzyme Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester