Ji Wei, Chen Xuyan, Zhengrong Chen, Yumin Hu, Huang Li, Qiu Yuhua
Department of Respiratory Diseases, Children's Hospital, Soochow University, Suzhou, People's Republic of China.
Int Immunopharmacol. 2008 Sep;8(9):1190-5. doi: 10.1016/j.intimp.2008.04.008. Epub 2008 May 21.
Allergic asthma is a chronic inflammatory disorder of airways, which is characterized by attacks provoked by exposure to so-called asthma triggers, such as pet dander, second-hand tobacco smoke, dust mites, and mold spores. B7-1 (CD80), perhaps one of the most studied co-stimulatory molecules involved in asthma, plays a key role in regulating allergen-induced T cell activation in asthma, probably through T cell recruitment and Th cell differentiation upon allergen provocation. The present study was designed to test the hypothesis that anti-B7-1 antibody has therapeutic effects in asthma by blocking B7-1/CD28 pathway. The asthma model was established by ovalbumin (OVA) sensitization and challenging in female Balb/c mice. One hour after the last induction, mice were sacrificed and whole lung lavage was conducted. Cell numbers in bronchoalveolar lavage fluid (BALF) were determined and the expression levels of IFN-gamma and IL-4 in supernatant were measured by an enzyme-linked immunosorbent assay method. Sedimental cells smears were stained with Wright's-Gimsa mixed coloring method. The B7-1 expression was detected by immunohistochemistry method with frozen tissue sections. The anti-B7-1 antibody treatment could alleviate asthmatic syndromes induced by OVA. The number of recoverable eosinophils in BALF in the anti-B7-1 antibody treated group was significantly lower than that in the control group (P<0.01) and the eosinophils peribronchial infiltration was remarkably reduced in anti-B7-1 treated asthmatic mice, based on histological evaluation. The treatment with the anti-B7-1 antibody induced IFN-gamma expression and decreased IL-4 expression, compared with the asthmatic control group (P<0.01). In conclusion, the anti-B7-1 antibody approach may provide a novel therapy for allergic asthma.
过敏性哮喘是一种气道慢性炎症性疾病,其特征是接触所谓的哮喘触发因素(如宠物皮屑、二手烟、尘螨和霉菌孢子)引发发作。B7-1(CD80)可能是哮喘研究最多的共刺激分子之一,在调节哮喘中变应原诱导的T细胞活化方面起关键作用,可能是通过变应原激发后募集T细胞和诱导Th细胞分化来实现。本研究旨在验证抗B7-1抗体通过阻断B7-1/CD28途径对哮喘具有治疗作用这一假说。通过对雌性Balb/c小鼠进行卵清蛋白(OVA)致敏和激发建立哮喘模型。在最后一次诱导后1小时,处死小鼠并进行全肺灌洗。测定支气管肺泡灌洗液(BALF)中的细胞数量,并采用酶联免疫吸附测定法测量上清液中IFN-γ和IL-4的表达水平。沉淀细胞涂片采用瑞氏-吉姆萨混合染色法染色。采用免疫组织化学方法检测冰冻组织切片中的B7-1表达。抗B7-1抗体治疗可减轻OVA诱导的哮喘症状。根据组织学评估,抗B7-1抗体治疗组BALF中可回收的嗜酸性粒细胞数量显著低于对照组(P<0.01),抗B7-1治疗的哮喘小鼠支气管周围嗜酸性粒细胞浸润明显减少。与哮喘对照组相比,抗B7-1抗体治疗诱导了IFN-γ表达并降低了IL-4表达(P<0.01)。总之,抗B7-1抗体方法可能为过敏性哮喘提供一种新的治疗方法。