Repeated antigenic challenge-induced airway hyperresponsiveness and airway inflammation in actively sensitized rats.

Repeated antigenic challenge-induced airway hyperresponsiveness and airway inflammation in actively sensitized rats.
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在主动致敏的大鼠中,反复抗原攻击诱导气道高反应性和气道炎症。

DOI:
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发表时间:
1993
期刊:
Japanese Journal of Pharmacology
影响因子:
--
通讯作者:
Y. Chiba
Y. Chiba
中科院分区:
--
文献类型:
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作者:
M. Misawa;Y. Chiba

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气道高反应性(AHR)是支气管哮喘的重要组成部分,但其机制尚不清楚。本研究旨在建立一种新的AHR实验动物模型。用DNP-Ascaris抗原(DNP-Asc)主动致敏的雄性Wistar大鼠在第一次免疫后8天通过吸入DNP-Asc进行攻击(单次抗原攻击)。另一个致敏组每48小时接受3次激发(重复抗原激发)。在麻醉状态下测定吸入乙酰胆碱(ACh)和神经激肽A(NKA)的气道反应性。用伊文思蓝(E.B.)测定气道微血管渗漏。单抗原激发后24小时,气道对ACh和NKA的反应性轻度增强,E. B.主支气管渗出增加。与此相反,气道对ACh和NKA的反应性和E. B.在反复抗原攻击后24小时,主支气管中的渗出显著增强得多。激发后大鼠离体主支气管条对ACh和5-羟色胺产生AHR。这些结果提示,反复抗原攻击可在体内和体外引起不同的AHR,气道炎症可能与AHR的发病机制密切相关。
Airway hyperresponsiveness (AHR) is a critical component in bronchial asthma, but the underlying mechanisms remain to be disclosed. Our present studies were performed to establish a new good experimental animal model of AHR. Male Wistar rats actively sensitized with DNP-Ascaris antigen (DNP-Asc) were challenged by inhaling DNP-Asc 8 days after the first immunization (single antigenic challenge). Another sensitization group received 3 challenges every 48 hr (repeated antigenic challenge). The airway responsiveness to inhalations of acetylcholine (ACh) and neurokinin A (NKA) were determined under anesthesia. The airway microvascular leakage was also determined with Evans blue (E.B.). At 24 hr after the single antigen challenge, the airway responsiveness to ACh and NKA were slightly enhanced, and the E.B. exudation was increased in the main bronchus. In contrast, the airway responsiveness to ACh and NKA and the E.B. exudation in the main bronchus were much more markedly enhanced 24 hr after the repeated antigenic challenge. The isolated main bronchial strip from the challenged rats had obtained AHR towards ACh and serotonin. These findings suggest that repeated antigenic challenge causes a distinct AHR, both in vivo and in vitro, and that the airway inflammation may be closely related to pathogenesis of AHR.
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