| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Mikio Teikyo Univ Schl Med, Associate Prof, 医学部, 助手 (10256034)
YAMADA Kazuhito Teikyo Univ Schl Med, Assistant Prof, 医学部, 助手 (40240006)
SAWAMOTO Shuichi Teikyo Univ Schl Med, Assistant Prof, 医学部, 助手 (30271290)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
In order to clarify the mechanisms for inducing bronchial asthma, we have focused on the expression of airway hyperresponsiveness as one of the characteristic features of asthma, and have been studying a murine model in which we can evaluate airway responsiveness to asetylcholine (Ach). In the present investigation performed for 2 years between 1994 and 1995, we tried to clarify how air pollutants, a group of important physiological stimuli, can induce airway hyperresponsiveness in our murine model especially by concentrating on cells and cytokines. Our results were as follows : 1) Administration into the airway with air pollutants such as nitric acid, a liquid transformation product of nitrogen dioxide, and diesel exhaust particulates (DEP) induced airway hyperresponsiveness in mice of both congenitally hyperresponsive (A/J) and hyporesponsive stains (Balb/c and C57Bl/6). 2) In a mast cell deficient strain, W/W^V, the augmentation of airway response with the air pollutants (nitric acid and DEP) was partially suppressed, suggesting that mast cells play some role but not a major one. 3) Neutralizing antibody to GM-CSF completely inhibited the augmentation of airway responsiveness to Ach with the airpollutants in A/J mice, suggesting a pivotal role of GM-CSF in the pathogenesis of airway hyperresponsiveness. Moreover, the expression of mRNA for GM-CSF was found to be upregulated in the lungs exposed to the airpollutants. 4) When we administered GM-CSSF into the airway in mice, airway responsiveness increased significantly, confirming the functional involvement of GM-CSF.5) Studies with neutralizing antibody to either IL-6 or IL-8 did not show significant inhibitory effects on airway hyperresponsiveness with air pollutants, suggesting that these factors do not play a central role in inducing airway hyperresponsiveness. We conclude that GM-CSF may play an important role in the pathogenesis of bronchial asthma.
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