Luccioli Stefano, Brody Dan T, Hasan Syed, Keane-Myers Andrea, Prussin Calman, Metcalfe Dean D
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
J Allergy Clin Immunol. 2002 Jul;110(1):117-24. doi: 10.1067/mai.2002.125828.
IL-4 is generated within hours after antigen lung challenge and influences events that take place early in the induction of pulmonary inflammation. However, the cells responsible for this early IL-4 production in the lung are unknown.
We sought to characterize the initial inflammatory events in the lung after antigen challenge and to identify cells responsible for producing IL-4 at early time points.
Mice were sensitized with ovalbumin or passive IgE and challenged intranasally. Histologic measures of inflammation were used, and lung tissue cytokine production was analyzed by means of RT-PCR. Cells producing IL-4 were characterized by means of in situ hybridization and flow cytometry.
IL-4 mRNA was detectable 100 minutes after challenge in sensitized animals. Blockade of this early IL-4 downregulated vascular cell adhesion molecule 1 mRNA expression and attenuated the early recruitment of eosinophils to the lung. CD4-depleted and mast cell-deficient mice both expressed early IL-4. Cellular analysis revealed the presence of IL-4 protein at 100 minutes exclusively in IgE(+) myeloid cells that did not express CD3, Kit, or I-A/I-E. Moreover, IL-4 production induced by means of passive IgE sensitization and abrogated in FcR gamma-chain-deficient mice supports the conclusion that this IL-4 production is dependent on IgE/gamma-chain interaction.
IL-4 production by an IgE/gamma-chain-dependent mechanism occurs rapidly after allergen challenge. At these early time points, IL-4 is produced by a myeloid cell with the characteristics of a mouse basophil (IgE(+), Kit(-), I-A/I-E(-)). These data thus suggest that strategies targeting basophils should be considered in the treatment of early lung inflammation.
白细胞介素-4（IL-4）在抗原攻击肺部数小时内产生，并影响肺部炎症诱导早期发生的事件。然而，肺部负责这种早期IL-4产生的细胞尚不清楚。
我们试图描述抗原攻击后肺部的初始炎症事件，并确定在早期时间点负责产生IL-4的细胞。
用卵清蛋白致敏小鼠或进行被动IgE致敏，然后经鼻攻击。采用炎症的组织学测量方法，并通过逆转录聚合酶链反应（RT-PCR）分析肺组织细胞因子的产生。通过原位杂交和流式细胞术对产生IL-4的细胞进行特征分析。
在致敏动物攻击后100分钟可检测到IL-4信使核糖核酸（mRNA）。阻断这种早期的IL-4可下调血管细胞黏附分子1 mRNA的表达，并减弱嗜酸性粒细胞向肺部的早期募集。CD4缺失和肥大细胞缺陷的小鼠均表达早期IL-4。细胞分析显示，在100分钟时，IL-4蛋白仅存在于不表达CD3、Kit或I-A/I-E的IgE（+）髓样细胞中。此外，通过被动IgE致敏诱导并在FcRγ链缺陷小鼠中消除的IL-4产生支持了这样的结论，即这种IL-4的产生依赖于IgE/γ链相互作用。
变应原攻击后，通过IgE/γ链依赖机制迅速产生IL-4。在这些早期时间点，IL-4由具有小鼠嗜碱性粒细胞特征（IgE（+）、Kit（-）、I-A/I-E（-））的髓样细胞产生。因此，这些数据表明，在治疗早期肺部炎症时应考虑针对嗜碱性粒细胞的策略。
