Studies on the pathogenesis of Loffler's syndrome induced by nematode infection

肠道线虫巴西尼波圆线虫感染可诱发洛夫勒综合征样肺炎。为了阐明I型超敏反应在线虫诱导的肺病变发病机制中的作用，我们研究了正常+/+和遗传肥大细胞缺陷Ws/Ws大鼠的肺部炎症、IgE反应、介质释放、血管通透性以及肺和/或气管中细胞因子mRNA的表达。感染后，+/+和Ws/Ws大鼠血液和肺门淋巴结的IgE抗体反应水平相似。线虫引起的肺炎在Ws/Ws大鼠肺中的严重程度明显减轻，并且Ws/Ws大鼠BALF中嗜酸性粒细胞浸润水平明显低于+/+动物。线虫抗原和埃文斯蓝染料静脉注射给线虫致敏的+/+和Ws/+大鼠，可诱导气管内的染料泄漏水平显著升高，而Ws/Ws大鼠则未显示出任何染料泄漏的增加。体外用线虫抗原刺激线虫致敏+/+动物的肺组织，显示组胺释放水平和白三烯C4产生水平明显高于Ws/Ws大鼠的肺组织。RT-PCR研究显示，感染后Ws/Ws和+/+大鼠肺组织中IL-2、IL-3、IL-4、IL-5、IL-6和IL-13 mRNA表达均升高。这些结果表明，肥大细胞对于气管和肺部血管通透性的立即型增加和介质释放的启动是必不可少的，ige -肥大细胞轴的激活似乎与线虫性肺炎的发生有关。细胞因子在肺炎调节中的作用仍有待阐明。

Infection with the intestinal nematode Nippostrongylus brasiliensis induces Loffler's syndrome-like pneumonitis. To elucidate the role of type I hypersensitivity in the pathogenesis of nematode-induced lung lesions, we studied lung inflammation, IgE responses, mediator releases, vascular permeability, and cytokine mRNA expressions in the lungs and/or trachea of normal +/+ and genetically mast cell-deficient Ws/Ws rats. After infection, +/+ and Ws/Ws rats showed similar levels of IgE antibody response in the blood and pulmonary hilar lymph nodes. Nematode-induced pneumonitis was significantly less severe in Ws/Ws rat lungs, and levels of eosinophil infiltration in BALF was significantly lower in Ws/Ws than in +/+ animals. Intravenous challenge with nematode antigen together with Evans blue dye to nematode-sensitized +/+ and Ws/+ rats induced significantly high levels of the dye leakage in the trachea, whereas Ws/Ws rats did not show any increases of dye leakage. Stimulation of lung tissues obtained from nematode-sensitized +/+ animals with nematode antigens in vitro showed significantly higher levels of histamine release and leukotriene C4 production than those from Ws/Ws rat lungs. RT-PCR studies showed that mRNA expressions of IL-2, IL-3, IL-4, IL-5, IL-6 and IL-13 were increased in the lung tissues of both Ws/Ws and +/+ rats after infection. These results indicate that mast cells are indispensable for the initiation of immediate-type increase of vascular permeability and mediator releases in the trachea and lungs, and that the activation of IgE-mast-cell axis seems to be relevant to the occurrence of nematode-induced pneumonitis. The role of cytokines for the modulation of pneumonitis still to be elucidated.