Mechanisms of exacerbation of asthma induced by RS virus infection and it's regulation due to drugs

人类呼吸道合胞病毒(RSV)在婴幼儿时期的感染会引起急性毛细支气管炎并加重哮喘。呼吸道合胞病毒感染时，嗜酸性粒细胞浸润可能是导致呼吸道阻塞的原因之一。我们假设RSV影响嗜酸性粒细胞功能。通过化学发光检测超氧阴离子(O(2)(-))的产生来评价嗜酸性粒细胞的激活。用流式细胞仪检测嗜酸性粒细胞表面CD11b的表达。虽然RSV不能诱导嗜酸性粒细胞产生O(2)(-)，但RSV能促进经血小板活化因子(PAF)刺激的嗜酸性粒细胞产生O(2)(-)。持续搅拌以防止嗜酸性粒细胞与试管表面的黏附，或用抗CD18抗体对细胞进行预处理，均可显著抑制增强作用，提示RSV对嗜酸性粒细胞的刺激作用依赖于通过β(2)-整合素的细胞黏附。事实上，RSV通过嗜酸性粒细胞增强PAF诱导的CD11b的表达。这些结果表明，RSV可增强PAF诱导的嗜酸性粒细胞CD11b表达和O(2)(-)生成。因此，呼吸道合胞病毒感染可能通过促进嗜酸性粒细胞释放介质而加重呼吸道炎症。

Human respiratory syncytial virus (RSV) infection in infancy and early childhood causes acute bronchiolitis and exacerbates bronchial asthma. Eosinophil infiltration may contribute to airway obstruction in RSV infection. We hypothesized that RSV affects eosinophil function. Eosinophil activation was evaluated by chemiluminescent detection of superoxide anion (O(2)(-)) generation. Expression of CD11b on eosinophils was determined by flow cytometry. Although RSV did not induce O(2)(-) generation by resting eosinophils, RSV enhanced O(2)(-) generation of eosinophils primed with platelet-activating factor (PAF). Enhancement was significantly inhibited by either continuous agitation to prevent eosinophil adhesion to test tube surfaces or by pretreating cells with anti-CD18 antibody, suggesting that the stimulatory effects of RSV on eosinophils depend on cell adhesion via beta(2)-integrins. In fact, RSV enhanced PAF-induced CD11b expression by eosinophils. These findings suggest that RSV enhances eosinophil CD11b expression and O(2)(-) generation induced by PAF. Thus, RSV infection may exacerbate airway inflammation by enhancing mediator release from eosinophils.