McKinley Laura, Kim Jiyoun, Bolgos Gerald L, Siddiqui Javed, Remick Daniel G
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Respir Res. 2006 Oct 17;7(1):129. doi: 10.1186/1465-9921-7-129.
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.
先前的基因分析表明，补体成分5基因编码区的缺失使小鼠因白细胞介素-12产生减少而更容易受到变应原诱导的气道高反应性（AHR）影响。我们研究了补体在哮喘样肺部炎症小鼠模型中的作用。
为了评估补体的作用，研究了C5充足或缺乏的B10小鼠。两组小鼠均用含有高水平蟑螂变应原的屋尘提取物（HDE）进行免疫和激发。用全身体积描记法测定气道高反应性。进行支气管肺泡灌洗（BAL）以确定肺细胞募集情况并测量炎症介质。测定肺匀浆中的介质和血浆IgE水平。还评估了肺组织学。
C5缺陷小鼠对乙酰甲胆碱激发的AHR增强，C5缺陷小鼠和C5充足小鼠的Penh分别比基线增加474%和91%，p<0.001。肺匀浆（LH）中的白细胞介素-12水平仅略有降低，C5充足和C5缺陷小鼠的BAL白细胞介素-12水平相当。然而，C5缺陷小鼠的BAL液中半胱氨酰白三烯水平显著更高，C5缺陷小鼠为1913±246 pg/ml，C5充足小鼠为756±232 pg/ml，p = 0.003。
这些数据表明，C5缺陷小鼠由于半胱氨酰白三烯产生增加而表现出增强的AHR。
