Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma
Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma
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DOI：
10.1016/s1567-5769(01)00084-4
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发表时间：
2001-09-01
影响因子：
5.6
通讯作者：
Agrawal, DK
中科院分区：
文献类型：
--
作者：
Hopfenspirger, MT;Parr, SK;Agrawal, DK
过敏原与遗传易感性相结合，驱使未分化的T细胞向2型T细胞转变。一些儿童感染可能会激活I型T细胞的产生。我们有理由推测，儿童感染的减少可能会使免疫平衡向2型T细胞转移，从而增加过敏的发生率。我们假设在致敏小鼠中预先暴露分枝杆菌抗原可以预防哮喘样疾病的发展。特别。我们检测了分枝杆菌抗原、卡介苗（BCG）疫苗和牛痘分枝杆菌对卵清蛋白（OVA）致敏和攻毒Balb/c小鼠抗原诱导的支气管收缩、气道对乙酰胆碱的高反应性、支气管肺泡灌洗嗜酸性粒细胞增多以及血浆IL-4和IL-12水平的影响。用OVA攻毒在3-5分钟内支气管收缩增加2-3倍，随后在60分钟后出现延迟反应，后者被卡介苗和母牛分枝杆菌显著减弱。卡介苗和母牛分枝杆菌可预防虫卵攻击后24小时气道对甲胆碱的高反应性。卡介苗和母牛分枝杆菌也能预防气道嗜酸性粒细胞增多。接种卡介苗或母牛分枝杆菌后，ova致敏小鼠血浆IL-12水平显著升高，IL-4水平显著降低。有趣的是，与母牛分枝杆菌相比，卡介苗组血浆IL-12显著增加，表明对卡介苗有更强的I型反应。这些数据支持我们的假设，并提示卡介苗和母牛分枝杆菌可能预防哮喘的潜在病理生理变化。(C) 2001 Elsevier Science B.V.版权所有
Allergens, in combination with genetic predisposition, drive undifferentiated T cells towards the type 2 T cells. Some childhood infections may activate the production of a type I T cell profile. It is reasonable to speculate that a decrease in childhood infections may increase the incidence of allergy by allowing the immune balance to shift towards the type 2 T cells. We hypothesized that pre-exposure of mycobacterial antigens in sensitized mice would prevent the development of asthma-like conditions. Specifically. we examined the effect of mycobacterial antigens, Bacillus Calmette-Guerin (BCG) vaccine and Mycobacterium vaccae, on antigen-induced bronchoconstriction, airway hyperresponsiveness to methacholine, bronchoalveolar lavage eosinophilia, and plasma IL-4 and IL-12 levels in ovalbumin (OVA)-sensitized and challenged Balb/c mice. Challenge with OVA produced a 2-3-fold increase in bronchoconstriction within 3-5 min, followed by a delayed response after 60 min, the latter of which was significantly attenuated by both BCG and M. vaccae. Airway hyperresponsiveness to methacholine 24 h after OVA challenge was prevented by BCG and M. vaccae. Airway eosinophilia was also prevented by BCG and M. vaccae. The plasma IL-12 levels were significantly increased and plasma IL-4 levels were significantly decreased following BCG or M. vaccae administration in OVA-sensitized and challenged mice. Interestingly, a significant increase in plasma IL-12 was observed with BCG as compared to M. vaccae administration, suggesting a stronger type I response to BCG. These data support our hypothesis and suggest that BCG and M. vaccae may prevent the underlying pathophysiological changes in asthma. (C) 2001 Elsevier Science B.V. All rights reserved.