Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice
Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice
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DOI：
10.1164/ajrccm.160.4.9806034
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发表时间：
1999-10-01
影响因子：
24.7
通讯作者：
Martin, TR
中科院分区：
文献类型：
--
作者：
Brewer, JP;Kisselgof, AB;Martin, TR
近交系小鼠品系之间在哮喘样肺部变化的易感性方面存在很大差异，这将为深入了解这些组成部分之间关系的性质提供帮助，并为研究其病因学的遗传学方法奠定基础。因此，我们研究了肺病理生理学和血清免疫球蛋白（IG）E反应的12个近交系小鼠腹腔内致敏卵清蛋白（OVA）和反复暴露于雾化OVA。最后一次暴露于OVA后1天，与假致敏小鼠相比，OVA致敏和暴露小鼠肺传导性降低50%（艾德（50）GL）所需的静脉乙酰甲胆碱（MCh）剂量降低0 - 2.7倍，具体取决于品系。在OVA致敏小鼠中，支气管肺泡灌洗（BAL）嗜酸性粒细胞占BAL细胞的3.3 +/- 3.1（SD）至91.2 +/- 5.0%，嗜酸性肺部炎症从不可检测到广泛和严重不等。在不同菌株中，OVA特异性IgE浓度范围从小于3 ng/ml至455 ng/ml。反应性的变化与菌株间的肺嗜酸性粒细胞增多显著相关（r > 0.70，p < 0.001），但与抗原特异性IgE水平无关（r = 0.55，p = 0.056）。这些结果表明，过敏原诱导的胆碱能反应性增强、肺嗜酸性粒细胞流入和血清抗原特异性IgE水平升高均由遗传决定，并且并不总是相关的。
Wide differences among inbred mouse strains in susceptibility to develop components of asthmalike pulmonary changes would provide insights into the nature of the relationships among those components and set the stage for genetic approaches to their etiology. We therefore examined pulmonary pathophysiological and serum immunoglobulin (Ig)E responses in mice of 12 inbred strains sensitized intraperitoneally with ovalbumin (OVA) and repeatedly exposed to aerosolized OVA. One day after the last OVA exposure the intravenous methacholine (MCh) dose required to reduce lung conductance by 50% (ED(50)GL) in OVA-sensitized and exposed mice was reduced by 0 to 2.7-fold, compared with sham-sensitized mice, depending on the strain. In OVA-sensitized mice, bronchoalveolar lavage (BAL) eosinophils comprised from 3.3 +/- 3.1 (SD) to 91.2 +/- 5.0% of BAL cells and eosinophilic pulmonary inflammation varied from being nondetectable to widespread and severe. OVA-specific IgE concentrations ranged from less than 3 ng/ml to 455 ng/ml in different strains. Shifts In responsiveness correlated significantly with pulmonary eosinophilia among strains (r > 0.70, p < 0.001) but not with antigen-specific IgE levels (r = 0.55, p = 0.056). These results demonstrate that allergen-induced enhancement of cholinergic responsiveness, pulmonary eosinophil influx, and elevations of serum antigen-specific IgE levels are each genetically determined and are not always associated.