Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
Int Arch Allergy Immunol. 2010;153(2):173-81. doi: 10.1159/000312635. Epub 2010 Apr 22.
Asthma and especially severe asthma affect women more frequently than men. Since asthma severity correlates with remodeling changes in the lung, a female propensity to remodeling could be expected. We studied whether our previous observation that female mice have more pronounced airway inflammation than males is associated with more pronounced remodeling in two models of chronic allergic asthma.
Male and female BALB/c mice were (1) sensitized and subsequently challenged with ovalbumin (OVA) for 4 weeks, or (2) exposed to house dust mite (HDM) for 5 weeks. In both models, allergic inflammation, remodeling, antigen-specific IgE and methacholine (MCh) responsiveness were assessed.
Females had higher antigen-specific serum IgE levels, higher numbers of eosinophils and were more responsive to MCh. In the OVA model, females also had higher levels of Th2 cytokines in lung tissue than males. Both sexes developed similar airway remodeling (smooth muscle layer thickness, collagen III deposition and goblet cell hyperplasia) in the two models.
Combining results of an OVA- and a HDM-induced mouse model of allergic airway inflammation, we have shown that more severe allergic inflammation in females is not accompanied with more pronounced airway remodeling.
哮喘,尤其是严重哮喘,比男性更频繁地影响女性。由于哮喘严重程度与肺部重塑变化相关,因此可以预期女性更容易发生重塑。我们研究了我们之前的观察结果,即雌性小鼠比雄性小鼠具有更明显的气道炎症,这是否与两种慢性变应性哮喘模型中更明显的重塑有关。
雄性和雌性 BALB/c 小鼠(1)用卵清蛋白(OVA)致敏,然后用 OVA 进行 4 周攻毒,或(2)用屋尘螨(HDM)暴露 5 周。在这两种模型中,评估了变应性炎症、重塑、抗原特异性 IgE 和乙酰甲胆碱(MCh)反应性。
雌性小鼠具有更高的抗原特异性血清 IgE 水平、更多的嗜酸性粒细胞,并且对 MCh 更敏感。在 OVA 模型中,雌性小鼠的肺组织中 Th2 细胞因子的水平也高于雄性小鼠。两种性别在两种模型中均发生相似的气道重塑(平滑肌层厚度、III 型胶原沉积和杯状细胞增生)。
综合 OVA 和 HDM 诱导的变应性气道炎症小鼠模型的结果,我们表明女性中更严重的变应性炎症并不伴有更明显的气道重塑。