Effect of ageing on pulmonary inflammation, airway hyperresponsiveness and T and B cell responses in antigen-sensitized and -challenged mice
Effect of ageing on pulmonary inflammation, airway hyperresponsiveness and T and B cell responses in antigen-sensitized and -challenged mice
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DOI：
10.1111/j.1365-2222.2007.02775.x
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发表时间：
2007-09-01
影响因子：
6.1
通讯作者：
Li, Xiu-Min
中科院分区：
文献类型：
--
作者：
Busse, Paula J.;Zhang, Teng Fei;Li, Xiu-Min
背景过敏性哮喘的几种病理特征(肺部炎症、嗜酸性粒细胞增多、粘液高分泌)随年龄的变化及其与气道高反应性(AHR)的关系尚不清楚。目的比较青年和老年小鼠过敏性哮喘模型中肺部炎症、粘液化生和AHR与年龄的关系。方法用卵蛋白(OVA)致敏和激发BALB/c小鼠。测定AHR、支气管肺泡液(BALF)、炎症细胞总数及分化程度。检测肺组织中主要的呼吸道粘蛋白相关基因MUC-5AC的定量聚合酶链式反应(MUC-5AC)，肺组织切片用高碘酸席夫(PAS)染色进行杯状细胞计数。用定量聚合酶链式反应检测肺组织细胞因子基因的表达，用酶联免疫吸附试验检测脾细胞培养的全身性细胞因子蛋白水平。采用酶联免疫吸附试验(ELISA)检测血清中抗原特异性IgE。结果老年和幼年OVA致敏/激发小鼠(OVA小鼠)均可形成AHR，幼龄OVA小鼠AHR明显高于老年OVA小鼠。然而，老年OVA小鼠的BALF嗜酸性粒细胞数量显著高于年轻OVA小鼠，肺组织学显示出更严重的炎症。老年OVA小鼠MUC-5AC的表达和PAS+染色的支气管上皮细胞数显著增加。与青年OVA小鼠相比，老年OVA小鼠肺组织中IL-5和干扰素-γ的mRNA表达增加，脾细胞培养的IL-5和干扰素-γ蛋白水平升高。结论虽然老年OVA小鼠抗原致敏/激发后肺部炎症和粘液化生程度较高，但AHR的升高幅度明显低于年轻OVA小鼠。与年轻小鼠(IL-4和IL-13升高)相比，抗原治疗在老年小鼠中产生了独特的细胞因子谱(升高的干扰素-γ和IL-5)。因此，老年动物对炎症的呼吸道反应减弱，可能代表与年龄相关的事件，导致不同的表型对抗原激发的反应。
Background The effect of ageing on several pathologic features of allergic asthma (pulmonary inflammation, eosinophilia, mucus hypersecretion), and their relationship with airway hyperresponsiveness (AHR) is not well characterized.Objective To evaluate lung inflammation, mucus metaplasia and AHR in relationship with age in murine models of allergic asthma comparing young and older mice.Methods Young (6 weeks) and older (6, 12, 18 months) BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and differential were measured. To evaluate mucus metaplasia, quantitative PCR for the major airway mucin-associated gene, MUC-5AC, from lung tissue was measured, and lung tissue sections stained with periodic acid-Schiff (PAS) for goblet-cell enumeration. Lung tissue cytokine gene expression was determined by quantitative PCR, and systemic cytokine protein levels by ELISA from spleen-cell cultures. Antigen-specific serum IgE was determined by ELISA. Results AHR developed in both aged and young OVA-sensitized/challenged mice (OVA mice), and was more significantly increased in young OVA mice than in aged OVA mice. However, BALF eosinophil numbers were significantly higher, and lung histology showed greater inflammation in aged OVA mice than in young OVA mice. MUC-5AC expression and numbers of PAS+ staining bronchial epithelial cells were significantly increased in the aged OVA mice. All aged OVA mice had increased IL-5 and IFN-gamma mRNA expression in the lung and IL-5 and IFN-gamma protein levels from spleen cell cultures compared with young OVA mice. OVA-IgE was elevated to a greater extent in aged OVA mice.Conclusions Although pulmonary inflammation and mucus metaplasia after antigen sensitization/challenge occurred to a greater degree in older mice, the increase in AHR was significantly less compared with younger OVA mice. Antigen treatment produced a unique cytokine profile in older mice (elevated IFN-gamma and IL-5) compared with young mice (elevated IL-4 and IL-13). Thus, the airway response to inflammation is lessened in ageing animals, and may represent age-associated events leading to different phenotypes in response to antigen provocation.