Female mice are more susceptible to the development of allergic airway inflammation than male mice
Female mice are more susceptible to the development of allergic airway inflammation than male mice
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DOI：
10.1111/j.1365-2222.2005.02362.x
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Hylkema, MN
中科院分区：
文献类型：
--
作者：
Melgert, BN;Postma, DS;Hylkema, MN
在人类中，青春期后女性哮喘的患病率高于男性。目的探讨雌鼠比雄鼠更易发生变应性哮喘的可能性及肺内的变应性免疫反应。方法比较雌、雄BALB/c小鼠的气道炎症反应，即乙酰甲胆碱（methacholine，MCh）反应性、血清IgE、细胞因子及肺内不同白细胞数。卵清蛋白（OVA）两次致敏，随后用OVA激发（OVA-小鼠）或磷酸盐缓冲盐水结果卵清蛋白刺激可显著增加MCh反应性、嗜酸性粒细胞、CD 4（+）T细胞、CD 4（+）/CD 25（+）T细胞、B细胞、以及辅助（Th）2细胞因子、总的和OVA特异性IgE的水平。然而，性别也有影响，雌性小鼠对OVA攻击的反应比雄性小鼠具有更高数量的嗜酸性粒细胞、CD 4（+）T细胞、B细胞以及IL-4、IL-13、IFN-γ、总IgE和OVA特异性IgE水平。相反，雌性PBS小鼠的调节性CD 4（+）/CD 25（+）T细胞的百分比显著低于雄性小鼠（雌性4.2 +/-0.2%vs.雄性5.3 +/-0.1%CD4（+）T细胞，P < 0.05）。雌性PBS-小鼠肺中调节性T细胞百分比降低可能表明，致敏期肺中这些细胞的水平对于多次OVA攻击后过敏性免疫应答的发生和/或进展是重要的。
Background In humans the prevalence of asthma is higher among females than among males after puberty. The reason for this phenomenon is not clear.Objective We tested the hypothesis that female mice are more susceptible to the development of allergic asthma than male mice and studied allergic immune responses in the lung.Methods We compared allergic airway inflammation, i.e. methacholine (MCh) responsiveness, serum IgE, and cytokines, and the number of the different leucocytes in lungs of male and female BALB/c mice, twice-sensitized to ovalbumin (OVA) and subsequently challenged with OVA (OVA-mice) or phosphate-buffered saline (PBS-mice) aerosols on days 24-26, 30, and 31.Results OVA challenge significantly increased MCh responsiveness, numbers of eosinophils, CD4(+) T cells, CD4(+)/CD25(+) T cells, B cells, and levels of Thelper (Th)2 cytokines, total, and OVA-specific IgE. There was, however, also an effect of gender, with female mice responding to OVA challenges with higher numbers of eosinophils, CD4(+) T cells, B cells, and levels of IL-4, IL-13, IFN-gamma, total, and OVA-specific IgE than male mice. In contrast, female PBS-mice had significantly lower percentages of regulatory CD4(+)/CD25(+) T cells than males (females 4.2 +/- 0.2% vs. males 5.3 +/- 0.1% of CD4(+) T cells, P < 0.05).Conclusions Female mice develop a more pronounced type of allergic airway inflammation than male mice after OVA challenge. The reduced percentage of regulatory T cells in the lungs of female PBS-mice may indicate that the level of these cells in the lung during the sensitization phase is important for the development and/or progression of an allergic immune response after multiple OVA challenges.