Study on the pathogenesis and treatment of airway rhinovirus infection-induced bronchial asthma

为探讨鼻病毒（rheinovirus，RV）感染诱发支气管哮喘急性发作的机制，我们检测了培养的人气管上皮细胞和粘膜下腺细胞中粘蛋白的产生、粘附在培养的人气管上皮细胞上的肺炎链球菌（Streptococcus pneumoniae，S.pneumoniae）的数量、RV感染对嗜酸性粒细胞趋化性的影响以及大环内酯类抗生素对RV感染的影响。我们发现RV感染诱导气管上皮细胞和粘膜下腺细胞产生包括MUC 5AC在内的多种粘蛋白mRNA，并增加了MUC 5AC在培养上清中的含量。RV感染后粘膜下腺细胞培养上清可增加嗜酸性粒细胞的趋化性。RV感染增加了粘附在上皮细胞上的肺炎链球菌的数量。调节活化、正常T细胞表达和分泌的抗体（RANTES）和粒细胞巨噬细胞集落刺激因子（GM-CSF），抑制嗜酸性粒细胞趋化性， ...更多信息 RV感染后培养上清中RANTES和GM-CSF含量增加。RV感染时粘膜下腺细胞释放的RANTES和GM-CSF可诱导嗜酸性粒细胞趋化。由于RV感染诱导产生血小板活化因子受体（PAF-R）、肺炎链球菌受体和PAF-R抑制剂减少肺炎链球菌数量，因此肺炎链球菌与上皮细胞的粘附可能与RV感染后的细菌性支气管肺炎有关。大环内酯类抗生素红霉素可降低培养气管上皮细胞上清液中RV滴度和RV RNA复制。RV主要类型受体细胞间粘附分子-1（ICAM-1）的产生减少和酸性内体数量减少可能是RV发病的原因。与红霉素对RV感染的抑制作用有关。红霉素还可以通过减少RV感染诱导的促炎细胞因子和ICAM-1的产生来调节气道炎症。少

To study the mechanisms of rhinovirus (RV) infection-induced bromchial asthma exacerbations, we examined mucin production in cultured human tracheal epithelial cells and submucosal gland cells, the number of Streptococcus pneumoniae (S.pneumoniae) adhering to the cultured human tracheal epithelial cells, the effects of RV infection on the eosinophil chemotaxis, and the effects of macrolide antibiotics on RV infection. We found that RV infection induced the production of various mucin mRNA including MUC5AC and increased MUC5AC content in supernatants in tracheal epithelial cells and submucosal gland cells. Culture supernatants of submucosal gland cells after RV infection increased the eosinophil chemotaxis. RV infection increased the number of S.pneumoniae adhering to the epithelial cells. Antibodies to regulate on activation, normal T cells expressed and secreted (RANTES) and granulocyte macrophage-colony stimulating factor (GM-CSF), inhibited the eosinophil chemotaxis, and reduced the … More content of RANTES and GM-CSF in culture supernatants increased after RV infection. RANTES and GM-CSF released from submucosal gland cells might induce eosinophil chemotaxis in RV infection. Because RV infection induced the production of a receptor for platelet activating factor (PAF-R), the receptor for S.pneumoniae, and a PAF-R inhibitor reduced the number of S.pneumoniae, adhesion of S.pneumoniae to the epithelial cells may be associated with the bacterial bronchopneumonia after RV infection. A macrolide antibiotic erythroycin reduced RV titers in supernatants and RV RNA replication in cultured tracheal epithelial cells. The reduced production of intercellular adhesion molecule-1 (ICAM-1), the receptor for major type RV and the reduced number of acidic endosomes might. be associated with the inhibitory effects of erythromycin on RV infection. Erythromycin may also modulate airway inflammation by reducing the production of pro-inflammatory cytokines and ICAM-1 induced by RV infection. Less