Bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (iBALT).
Bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (iBALT).
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DOI：
10.1038/labinvest.2015.72
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发表时间：
2015-08
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影响因子：
--
通讯作者：
Sell S
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文献类型：
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作者：
Guest IC;Sell S
我们通过免疫组织学系统地检查了一些广泛使用的哮喘小鼠模型的肺。这些模型包括多次注射可溶性卵清蛋白(OVA)或将OVA与明矾一起注射致敏，然后每隔3天进行三次鼻腔或气雾剂激发。单次激发后24小时内，动脉壁纤维素样坏死，免疫球蛋白和卵清蛋白沉积，嗜酸性多形核细胞浸润，持续约3天，随后支气管周围B细胞浸润，轻度可逆性杯状细胞肥大。2次激发后6小时出现严重嗜酸性血管炎，72小时后开始下降；B细胞增殖、杯状细胞肥大和增生(GCHTH)及支气管平滑肌肥大复发更为显著。在3次攻击后，诱导的支气管相关淋巴组织(IBALT)形成、GCHTH和平滑肌肥大显著增加。支气管灌洗液中存在Th2细胞因子水平升高：IL-4、IL-5和IL-13。致敏的小鼠有沉淀抗体和ARTHUS皮肤反应，但也产生了显着水平的OVA IgE抗体，但仅在攻击后1周。我们认为，免疫复合物介导的嗜酸性血管炎和iBALT的形成是这些模型诱导的哮喘样肺损害的先兆。Th2细胞因子的升高最有可能导致类似于人类哮喘的支气管病变。然而，肥大细胞激活的特应性机制是不太可能的，因为我们通过甲苯胺蓝和异染色染色法只发现了几个假定的肥大细胞，局限于主干支气管的最近端，在剩余的主干支气管或肺周围没有肥大细胞。
We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery.