Cates Elizabeth C, Fattouh Ramzi, Wattie Jennifer, Inman Mark D, Goncharova Susanna, Coyle Anthony J, Gutierrez-Ramos José-Carlos, Jordana Manel
Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, Division of Respiratory Diseases and Allergy, McMaster University, 1200 Main Street, Hamilton, Ontario, Canada L8S 3Z5.
J Immunol. 2004 Nov 15;173(10):6384-92. doi: 10.4049/jimmunol.173.10.6384.
It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production.
现已充分证实，被动吸入卵清蛋白（OVA）会导致免疫耐受状态。因此，为引发过敏致敏，研究人员不得不设计替代策略，例如在强效佐剂存在的情况下全身递送OVA，而这与人类接触和致敏过敏原的方式不同。这些研究的目的是调查对经鼻递送纯化屋尘螨（HDM）提取物的免疫炎症反应，并评估GM-CSF在此过程中的作用。将HDM每日给予BALB/c小鼠，持续10天。最后一次暴露后，处死小鼠，进行支气管肺泡灌洗并获取样本。分别通过实时定量PCR和ELISA评估淋巴结、肺和脾中Th2相关分子的表达/产生情况。采用这种暴露方案，单独暴露于HDM会基于Th2效应分子的表达/产生以及气道嗜酸性粒细胞炎症产生Th2致敏。流式细胞术分析显示肺中抗原呈递细胞（APC）扩增并激活，以及活化的Th2效应细胞流入。此外，这种炎症伴有气道高反应性和强烈的记忆驱动免疫反应。最后，给予抗GM-CSF中和抗体显著降低了肺和脾中的免疫炎症反应。因此，经鼻递送HDM会导致Th2致敏和气道嗜酸性粒细胞炎症，这似乎至少部分是由内源性GM-CSF产生介导的。
