Siddiqui S, Morris J, Avery N, Wyand S, Rood D, Silbart L K
Department of Animal Science, Center of Excellence for Vaccine Research, University of Connecticut, Storrs, CT 06269-2101, USA.
Clin Exp Allergy. 2008 Aug;38(8):1381-90. doi: 10.1111/j.1365-2222.2008.03009.x. Epub 2008 Jun 4.
Eosinophilic infiltration into the airways is frequently associated with allergic asthma; however, the role of antigen deposition in mediating this phenomenon has not been studied in detail.
Using a murine model of ovalbumin (OVA) allergy, we examined how differential deposition of OVA during antigen challenge affects pulmonary eosinophilia, immune response and airway hyper-reactivity (AHR).
Differential allergen deposition to the upper respiratory tract (URT) alone or combined upper and lower respiratory tract (ULRT) was accomplished by administering OVA intranasally to either anaesthetized or unanaesthetized mice, respectively. BALB/c mice (6-7 weeks old) were sensitized with OVA-alum via the intraperitoneal route, and then challenged intranasally using OVA, with or without anaesthesia. AHR, enumeration of inflammatory cells and quantitative measurement of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF), lung histopathology and immune responses were subsequently assessed.
In sensitized animals challenged via the ULRT route, a profound eosinophilia and goblet cell hyperplasia was observed in lung tissue. Conversely, sensitized mice receiving an identical challenge dose via the URT route alone exhibited only negligible levels of inflammation. Interestingly, AHR and OVA-specific IgG(1) and IgE systemic responses were comparable between the two groups.
This study indicates that direct exposure of allergen in the deep lung is highly correlated with airway eosinophilia and lung inflammation, but does not correlate with AHR or immune response.
嗜酸性粒细胞浸润气道常与过敏性哮喘相关;然而,抗原沉积在介导这一现象中的作用尚未得到详细研究。
利用卵清蛋白(OVA)过敏的小鼠模型,我们研究了抗原激发过程中OVA的差异沉积如何影响肺部嗜酸性粒细胞增多、免疫反应和气道高反应性(AHR)。
通过分别向麻醉或未麻醉的小鼠鼻内给予OVA,实现变应原单独向上呼吸道(URT)或联合上下呼吸道(ULRT)的差异沉积。6-7周龄的BALB/c小鼠通过腹腔途径用OVA-明矾致敏,然后用OVA鼻内激发,有无麻醉均可。随后评估AHR、支气管肺泡灌洗液(BALF)中炎性细胞计数、炎性细胞因子和趋化因子的定量测量、肺组织病理学和免疫反应。
在通过ULRT途径激发的致敏动物中,在肺组织中观察到严重的嗜酸性粒细胞增多和杯状细胞增生。相反,仅通过URT途径接受相同激发剂量的致敏小鼠仅表现出可忽略不计的炎症水平。有趣的是,两组之间的AHR以及OVA特异性IgG(1)和IgE全身反应相当。
本研究表明,过敏原在深部肺脏中的直接暴露与气道嗜酸性粒细胞增多和肺部炎症高度相关,但与AHR或免疫反应无关。