Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
Yonsei Med J. 2012 May;53(3):593-602. doi: 10.3349/ymj.2012.53.3.593.
Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice.
Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice.
Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation.
Endotoxin in CR extracts may not be essential to the development of airway inflammation.
蟑螂（CR）是一种重要的吸入性过敏原，可诱发过敏性哮喘。然而，蟑螂提取物诱导气道过敏性炎症的机制以及内毒素在其中的作用，在气道炎症的发展过程中尚不清楚。在本研究中，我们评估了内毒素是否是蟑螂诱导气道过敏性炎症发展所必需的。
通过分别向 BALB/c 野生型小鼠的鼻腔内给予蟑螂提取物、添加内毒素的蟑螂提取物或内毒素耗尽的蟑螂提取物，诱导气道过敏性炎症。还使用 Toll 样受体-4（TLR-4）突变型（C3H/HeJ）和野生型（C3H/HeN）小鼠评估了蟑螂诱导的炎症。
蟑螂提取物的鼻腔内给药显著地以剂量依赖性方式诱导气道高反应性（AHR）、嗜酸性粒细胞和中性粒细胞性气道炎症以及呼吸上皮细胞的杯状细胞增生。内毒素与蟑螂过敏原一起添加减弱了嗜酸性粒细胞炎症、白细胞介素（IL）-13 水平和呼吸上皮的杯状细胞增生，但不影响 AHR 的发展。与单独的 CR 相比，CR 提取物中的内毒素耗竭并没有减轻 BAL 液中的嗜酸性粒细胞炎症和淋巴细胞增多、肺中的 AHR 和 IL-13 表达。与野生型小鼠相比，TLR-4 突变型小鼠中 CR 提取物单独诱导的 AHR、嗜酸性粒细胞炎症和杯状细胞增生的减弱并无差异。此外，热灭活的 CR 提取物给药诱导的 AHR 和嗜酸性粒细胞炎症减弱。
蟑螂提取物中的内毒素可能不是气道炎症发展所必需的。
