Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization
Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization
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DOI：
10.1067/mai.2003.1460
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发表时间：
2003-05-01
影响因子：
14.2
通讯作者：
Jordana, M
中科院分区：
文献类型：
--
作者：
Cates, EC;Gajewska, BU;Jordana, M
背景资料：过敏性气道炎症的传统模型涉及腹膜内给予卵清蛋白与化学佐剂（通常是氢氧化铝）联合，以产生过敏性气道炎症。在这里，我们研究了呼吸道粘膜暴露于豚草提取物在没有化学佐剂的情况下对过敏反应产生的影响。目的：我们试图通过粘膜致敏来建立豚草诱导的过敏性气道炎症的小鼠模型，并研究GM-CSF在此过程中的作用。将豚草鼻内递送至富含GM-CSF的气道微环境，其通过重组GM-CSF的多次共施用或携带GM-CSF的腺病毒载体的单次递送来实现。CSF转基因。施用纯化的豚草提取物导致T（H）2致敏（而不是吸入耐受性），伴随轻度气道炎症、适度临床症状和脾细胞对豚草再刺激的T（H）2细胞因子的适度产生。抗GM-CSF抗体与豚草联合给药可减少T（H）2相关细胞因子的产生。通过用GM-CSF富集气道微环境来放大这些反应。在这些条件下，所有T（H）2相关的免疫炎症反应以及临床反应都显著增强。为了研究这些作用的机制，我们通过流式细胞术检测了肺单核细胞，并检测到抗原呈递细胞，特别是树突状细胞的显著扩增，以及这些抗原呈递细胞的显著增加的活化，如通过B7分子，特别是B7.2的表达所证明的。GM-CSF在豚草过敏性肠炎症反应的产生中起重要作用。
Background: Conventional models of allergic airway inflammation involve intraperitoneal administration of ovalbumin in conjunction with a chemical adjuvant (generally aluminum hydroxide) to generate allergic airways inflammation. Here we have investigated the effect of respiratory mucosal exposure to a ragweed extract in the absence of chemical adjuvant on the generation of allergic responses.Objectives: We sought to develop a mouse model of ragweed-induced allergic airway inflammation through mucosal sensitization and to investigate the role of GM-CSF in this process.Methods: Ragweed was delivered intranasally to an airway microenvironment enriched with GM-CSF, which was achieved by means of either multiple coadministrations of recombinant GM-CSF or a single delivery of an adenoviral vector carrying the GM-CSF transgene.Results: Administration of a purified ragweed extract leads to T(H)2 sensitization (and not inhalation tolerance) accompanied by mild airway inflammation, modest clinical symptoms, and moderate production of T(H)2 cytokines by splenocytes on ragweed restimulation. The administration of anti-GM-CSF antibodies in conjunction with ragweed diminished T(H)2-associated cytokine production. These responses were amplified by enriching the airway microenvirimment with GM-CSF. Under these conditions, all T(H)2-associated immune-inflamniatory responses, as well as the clinical responses, were considerably enhanced. To investigate the mechanism underlying these effects we examined lung mononuclear cells by means of flow cytometry and detected a substantial expansion of antigen-presenting cells, particularly dendritic cells, as well as a substantially increased activation of these antigen-presenting cells, as demonstrated by the expression of B7 molecules, particularly B7.2.Conclusion: GM-CSF plays an important role in the generation of allergic inumme-inflammatory responses to ragweed.