Kim J, Merry A C, Nemzek J A, Bolgos G L, Siddiqui J, Remick D G
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Immunol. 2001 Sep 1;167(5):2808-15. doi: 10.4049/jimmunol.167.5.2808.
Asthma represents a serious health problem particularly for inner city children, and recent studies have identified that cockroach allergens trigger many of these asthmatic attacks. This study tested the concept that asthma-like pulmonary inflammation may be induced by house dust containing cockroach allergens. An aqueous extract was prepared from a house dust sample containing endotoxin and high levels of cockroach allergens. BALB/c mice were immunized with the house dust extract (HDE) and received two additional pulmonary challenges. Bronchoalveolar lavage (BAL) eosinophil counts and eotaxin levels were significantly increased in immunized mice exposed to the HDE, whereas neutrophils were the predominant BAL inflammatory cell in the unimmunized mice. Kinetics studies in immunized mice demonstrated a peak pulmonary inflammatory response 48 h after the last challenge. The allergic response in this model was further confirmed by histological and physiological studies demonstrating a significant influx of eosinophils and lymphocytes in the peribronchial area, and severe airway hyperreactivity through whole-body plethysmography. The specificity of the response was established by immunizing with HDE and challenging with purified cockroach allergen, which induced pulmonary eosinophilia and airway hyperreactivity. Ab inhibition of eotaxin significantly inhibited the number of BAL eosinophils. These data describe a novel murine model of asthma-like pulmonary inflammation induced by house dust containing endotoxin and cockroach allergens and further demonstrate that eotaxin represents the principal chemoattractant for the recruitment of the pulmonary eosinophils.
哮喘是一个严重的健康问题,尤其对市中心区的儿童而言,并且最近的研究已经确定蟑螂过敏原会引发许多此类哮喘发作。本研究检验了一种观念,即含有蟑螂过敏原的室内灰尘可能诱发类似哮喘的肺部炎症。从一份含有内毒素和高水平蟑螂过敏原的室内灰尘样本中制备了水提取物。用该室内灰尘提取物(HDE)对BALB/c小鼠进行免疫,并对其进行另外两次肺部激发。暴露于HDE的免疫小鼠支气管肺泡灌洗(BAL)嗜酸性粒细胞计数和嗜酸性粒细胞趋化因子水平显著升高,而在未免疫小鼠中,中性粒细胞是BAL中主要的炎性细胞。对免疫小鼠的动力学研究表明,在最后一次激发后48小时出现肺部炎症反应高峰。组织学和生理学研究进一步证实了该模型中的过敏反应,这些研究显示支气管周围区域有大量嗜酸性粒细胞和淋巴细胞流入,并且通过全身体积描记法显示有严重的气道高反应性。通过用HDE免疫并用纯化的蟑螂过敏原进行激发来确定反应的特异性,后者可诱发肺部嗜酸性粒细胞增多和气道高反应性。抗嗜酸性粒细胞趋化因子抗体显著抑制了BAL嗜酸性粒细胞的数量。这些数据描述了一种由含有内毒素和蟑螂过敏原的室内灰尘诱发的类似哮喘的肺部炎症的新型小鼠模型,并进一步证明嗜酸性粒细胞趋化因子是募集肺部嗜酸性粒细胞的主要趋化因子。