TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice
TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice
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DOI：
10.1016/j.jaci.2006.11.701
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发表时间：
2007-03-01
影响因子：
14.2
通讯作者：
Galli, Stephen J.
中科院分区：
文献类型：
--
作者：
Nakae, Susumu;Lunderius, Carolina;Galli, Stephen J.
背景：TNF 被认为会导致哮喘气道高反应性 (AHR) 和气道炎症。然而，对 TNF 缺陷或 TNF 受体缺陷小鼠的研究尚未清楚地了解 TNF 在与小鼠过敏性炎症相关的 AHR 中的作用。 目的：我们使用遗传学方法研究 TNF 对 C57BL/6 背景小鼠中抗原诱导的 AHR 和气道炎症的贡献。 方法：我们分析了 C57BL/6 野生型和 TNF-/- 小鼠中气道过敏性炎症的特征，包括抗原诱导的 AHR，使用 2 种不同的方法使小鼠对卵清蛋白 (OVA) 敏感。结果：在对给予氢氧化铝（明矾）佐剂的 OVA 敏感的小鼠中，这些小鼠会产生不依赖于 IgE 和不依赖于肥大细胞的过敏性炎症和 AHR，我们发现 C57BL/6-TNF-/- 与野生型小鼠相比，OVA 诱导的 AHR 没有显着差异。相比之下，在对不含明矾的 OVA 敏感的小鼠中，C57BL/6-TNF-/- 小鼠会发生明显肥大细胞依赖性的过敏性炎症，与野生型小鼠相比，OVA 诱导的乙酰甲胆碱 AHR 显着降低；支气管肺泡灌洗液中淋巴细胞、中性粒细胞和嗜酸性粒细胞的数量；肺组织中髓过氧化物酶、嗜酸性粒细胞过氧化物酶以及细胞因子 IL-4、IL-5 和 IL-17 的水平；结论：在用不含明矾的 OVA 免疫小鼠诱导的肺部过敏性炎症中，TNF 显着促进了反应的几个特征，包括抗原诱导的炎症和 AHR。临床意义：我们在小鼠中的研究结果支持了 TNF 可以促进与哮喘相关的过敏性炎症和 AHR 的假设。
Background: TNF is thought to contribute to airway hyperreactivity (AHR) and airway inflammation in asthma. However, studies with TNF-deficient or TNF receptor-deficient mice have not produced a clear picture of the role of TNF in the AHR associated with allergic inflammation in the mouse.Objective: We used a genetic approach to investigate the contributions of TNF to antigen-induced AHR and airway inflammation in mice on the C57BL/6 background.Methods: We analyzed features of airway allergic inflammation, including antigen-induced AHR, in C57BL/6 wild-type and TNF-/- mice, using 2 different methods for sensitizing the mice to ovalbumin (OVA).Results: In mice sensitized to OVA administered with the adjuvant aluminum hydroxide (alum), which develop IgE-independent and mast cell-independent allergic inflammation and AHR, we found no significant differences in OVA-induced AHR in C57BL/6-TNF-/- versus wild-type mice. By contrast, in mice sensitized to OVA without alum, which develop allergic inflammation that is significantly mast cell-dependent, C57BL/6-TNF-/- mice exhibited significant reductions versus wildtype mice in OVA-induced AHR to methacholine; numbers of lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid; levels of myeloperoxidase, eosinophil peroxidase, and the cytokines IL-4, IL-5, and IL-17 in lung tissue; and histologic evidence of pulmonary inflammation.Conclusion: In pulmonary allergic inflammation induced in mice immunized with OVA without alum, TNF significantly contributes to several features of the response, including antigen-induced inflammation and AHR.Clinical implications: Our findings in mice support the hypothesis that TNF can promote the allergic inflammation and AHR associated with asthma.