Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice.
Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice.
复制标题
DOI：
10.1186/1465-9921-7-129
复制
发表时间：
2006-10-17
影响因子：
5.8
通讯作者：
Remick DG
中科院分区：
文献类型：
--
作者：
McKinley L;Kim J;Bolgos GL;Siddiqui J;Remick DG
先前的遗传分析表明，补体成分5基因编码区域的缺失使小鼠更容易因IL-12产生减少而产生过敏原诱导的气道高反应性（AHR）。我们研究了补体在哮喘样肺部炎症小鼠模型中的作用。为了评价补体B10的作用，我们研究了C5充足或缺乏的小鼠。两组小鼠都接种了含有高水平蟑螂过敏原的屋尘提取物（HDE）。气道高反应性采用全身脉搏图测定。支气管肺泡灌洗（BAL）测定肺细胞募集和测量炎症介质。检测肺匀浆介质和血浆IgE水平。肺组织学也进行了评估。c5缺陷小鼠对甲基胆碱的AHR增强，c5缺陷小鼠和c5充足小鼠的AHR分别比基线Penh增加474%和91%，p < 0.001。肺匀浆（LH）中IL-12水平仅轻微降低，BAL IL-12在c5充足和c5缺乏的小鼠中相当。然而，c5缺陷小鼠BAL液中半胱氨酸-白三烯水平显著升高，C5d组为1913 +/- 246 pg/ml， c5 -充足组为756 +/- 232 pg/ml， p = 0.003。这些数据表明，由于半胱氨酸-白三烯的产生增加，c5缺陷小鼠的AHR增加。
Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation. In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied. Both groups of mice immunized and challenged with a house dust extract (HDE) containing high levels of cockroach allergens. Airways hyper-reactivity was determined with whole-body plesthysmography. Bronchoalveolar lavage (BAL) was performed to determine pulmonary cellular recruitment and measure inflammatory mediators. Lung homogenates were assayed for mediators and plasma levels of IgE determined. Pulmonary histology was also evaluated. C5-deficient mice showed enhanced AHR to methylcholine challenge, 474% and 91% increase above baseline Penh in C5-deficient and C5-sufficient mice respectively, p < 0.001. IL-12 levels in the lung homogenate (LH) were only slightly reduced and BAL IL-12 was comparable in C5-sufficient and C5-deficient mice. However, C5-deficient mice had significantly higher cysteinyl-leukotriene levels in the BAL fluid, 1913 +/- 246 pg/ml in C5d and 756 +/- 232 pg/ml in C5-sufficient, p = 0.003. These data demonstrate that C5-deficient mice show enhanced AHR due to increased production of cysteinyl-leukotrienes.