Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice
Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice
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DOI：
10.1016/j.jaci.2007.02.046
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发表时间：
2007-07-01
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;Ho, Lien H.;Galli, Stephen J.
背景：肥大细胞、IgE 和 TNF 与人类特应性哮喘有关，在用不含明矾的 OVA 致敏的小鼠中，对卵清蛋白 (OVA) 激发诱导的过敏性气道炎症有显着影响。然而，尚不清楚肥大细胞在多大程度上是该小鼠模型中 TNF 的重要来源。目的：我们研究了肥大细胞来源的 TNF 在 OVA 诱导的气道高反应性 (AHR) 和过敏性气道炎症的肥大细胞依赖性模型中的重要性。方法：在 C57BL/6J 野生型小鼠、肥大细胞缺陷型 C57BL/6J-Kit(W-sh/W-sh) 小鼠中分析了该气道炎症模型的特征。小鼠和系统移植了来自 C57BL/6J 野生型或 C57BL/6J-TNF-/- 小鼠的骨髓源性培养肥大细胞的 C57BL/6J Kit(W-sh/W-sh) 小鼠。 结果：与野生型小鼠相比，肥大细胞缺陷 Kit(W-sh/W-sh) 小鼠中卵清蛋白诱导的 AHR 和气道炎症显着减少。相比之下，移植了野生型但未移植 TNF-/- 骨髓源性培养肥大细胞的 Kit(W-sh/W-sh) 小鼠表现出与野生型小鼠中观察到的反应非常相似。在致敏阶段，肥大细胞和肥大细胞源性 TNF 不需要诱导 OVA 特异性记忆 T 细胞，但在攻击阶段显着增强淋巴细胞募集和 T(H)2 细胞因子产生。结论：肥大细胞源性 TNF 对肥大细胞依赖性和 IgE 依赖性、OVA 诱导的小鼠过敏性炎症和 AHR 的发病机制有显着贡献，可能部分是通过增强淋巴细胞募集和 T(H)2 细胞因子产生来实现的。临床意义：我们的研究结果小鼠支持了肥大细胞源性 TNF 可以促进哮喘过敏性炎症和 AHR 的假设。
Background: Mast cells, IgE, and TNF, which have been implicated in human atopic asthma, contribute significantly to the allergic airway inflammation induced by ovalbumin (OVA) challenge in mice sensitized with OVA without alum. However, it is not clear to what extent mast cells represent a significant source of TNF in this mouse model.Objective: We investigated the importance of mast cell-derived TNF in a mast cell-dependent model of OVA-induced airway hyperreactivity (AHR) and allergic airway inflammation.Methods: Features of this model of airway inflammation were analyzed in C57BL/6J-wild-type mice, mast cell-deficient C57BL/6J-Kit(W-sh/W-sh) mice, and C57BL/6J Kit(W-sh/W-sh) mice that had been systemically engrafted with bone marrow-derived cultured mast cells from C57BL/6J-wild-type or C57BL/6J-TNF-/- mice.Results: Ovalbumin-induced AHR and airway inflammation were significantly reduced in mast cell-deficient Kit(W-sh/W-sh) mice versus wild-type mice. By contrast, Kit(W-sh/W-sh) mice that had been engrafted with wild-type but not with TNF-/- bone marrow-derived cultured mast cells exhibited responses very similar to those observed in wild-type mice. Mast cells and mast cell-derived TNF were not required for induction of OVA-specific memory T cells in the sensitization phase, but significantly enhanced lymphocyte recruitment and T(H)2 cytokine production in the challenge phase.Conclusion: Mast cell-derived TNF contributes significantly to the pathogenesis of mast cell-dependent and IgE-dependent, OVA-induced allergic inflammation and AHR in mice, perhaps in part by enhancing lymphocyte recruitment and T(H)2 cytokine production.Clinical implications: Our findings in mice support the hypothesis that mast cell-derived TNF can promote allergic inflammation and AHR in asthma.