DEVELOPMENT OF AN EXPERIMENTAL ALLERGIC RHINITIS MODEL AND ANALYSIS OF MECHANISMS OF THE DISEASE
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||KYOTO PHARMACEUTICAL UNIVERSITY|
KOHNO Shigekatsu KYOTO PHARMACEUTICAL UNIVERSITY DEPARTMENT OF PHARMACOLOGY, PROFESSOR, 薬理学教室, 教授 (50082988)
NABE Takeshi KYOTO PHARMACEUTICAL UNIVERSITY DEPARTMENT OF PHARMACOLOGY, LECTURER, 薬理学教室, 講師 (40228078)
|Project Period (FY)
1997 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥2,700,000 (Direct Cost : ¥2,700,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
|Keywords||Alloergy / Rhinitis / Cedar Pollen / Upper Airways / Nasal Blockage / Sneeze / lgE / Histamine|
For development of an experimental nasal allergy model, guinea-pigs were sensitized by intranasal application of Japanese cedar pollen extract +Al(OH)ィイD23ィエD2 and then challenged by quantitative inhalation of the pollen once a week for a long term. Furthermore, mechanisms of the disease were analyzed.
1. Development of the model
(1) Biphasic nasal blockage was observed with their peaks at 1-2 and 4-6 hr after challenges.
(2) Sneeze was induced immediately after challenges.
(3) Titers of antigen-specific γ1 and lgE antibodies elevated with repetition of the challenges.
(4) A newly developed nasal cavity lavage demonstrated that Immediate albumin leakage and histamine release, and late eosinophil influx were induced in the cavity after the challenge.
(5) The sensitized-challenged animal showed apparent nasal blockage to intranasal instillation of considerable low concentrations of histamine and leukotriene DィイD24ィエD2 compared with non-sensitized animal.
2. Analyses of mechanisms of the nasal h
yperresponsiveness to histamine
(1) Degree of the hyperresponsiveness augmented with repetition of the challenge. The hyperresponsiveness was observed already at the 4th hr followed by diminishment at the 7th day.
(2) The increase of the responsiveness was blocked by mepyramine but not by atropine.
(3) The histamine-induced nasal blockage in the sensitized-challenged animal reached its peak at the 10th min and disappeared at the 60th min.
(4) Naphazoline potently lowered the increase of nasal resistance by histamine, but the degree did not reached to the level observed in the non-sensitized-naphazoline-treated animal.
(5) Histamine induced slight but significant plasma leakage in the lamina propria and the luminal entry of the sensitized-challenged animal.
In this study, an experimental nasal allergy model showing similar symptoms to the patients with allergic rhinitis was established. It is indicated that the hyperresponsiveness in mainly due to the increase of dilatation of the nasal mucosal vessels. Less
Research Output (8results)