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

线虫感染所致洛夫勒综合征发病机制的研究

• 批准号: 07457067
• 负责人: ARIZONO Naoki
• 金额: $ 3.71万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457067/
• 关键词: nematode; Ws; Ws rat; lung; mast cell; IgE; vascular peameability; leukotriene; cytokine; Nippostrongylus brasiliensis; ヒスタミン; マスト細胞欠損ラット; IgE抗体; I型過敏症

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.

巴西日本圆线虫感染可引起Loffler综合征样肺炎为了阐明I型超敏反应在线虫引起的肺部病变的发病机制中的作用，我们研究了正常+/+和遗传性肥大细胞缺陷的Ws/Ws大鼠的肺和/或气管中的肺部炎症、IgE反应、介质释放、血管通透性和细胞因子mRNA表达。感染后，+/+和Ws/Ws大鼠在血液和肺门淋巴结中显示出相似水平的IgE抗体反应。Ws/Ws大鼠肺中线虫诱导的肺炎显著较轻，Ws/Ws大鼠BALF中嗜酸性粒细胞浸润水平显著低于+/+动物。线虫致敏+/+和Ws/+大鼠静脉注射线虫抗原和Evans蓝染料后，气管内染料渗漏明显增加，而Ws/Ws大鼠气管内染料渗漏无明显增加。从线虫致敏+/+动物与线虫抗原在体外获得的肺组织的刺激表现出显着更高的组胺释放和白三烯C4的生产水平比那些从Ws/Ws大鼠肺。RT-PCR结果显示，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的mRNA表达均增加。这些结果表明，肥大细胞是必不可少的启动立即型增加血管通透性和介质释放在气管和肺，IgE-肥大细胞轴的激活似乎是相关的线虫引起的肺炎的发生。细胞因子对肺炎的调节作用仍有待阐明。

项目成果

Arizono, N.: "Lung granulomatous response induced by infection with the intestinal nematode Nippostrongylus brasiliensis is suppressed in mast cell-deficient Ws/Ws rats." Clin. Exp. Immunol. 106. 55-61 (1996)

Arizono, N.：“在肥大细胞缺陷的 Ws/Ws 大鼠中，由肠道线虫巴西圆线虫感染引起的肺肉芽肿反应受到抑制。”

Arizono Naoki: "Lung granulomatous response induced by infection with the intestinal nematode Nippostrongylus brosiliensis is suppresed in mast cell-deficient Ws/Ws rats." Clinical and Experimental Immunology. 106. 55-61 (1996)

Arizono Naoki：“在肥大细胞缺陷的 Ws/Ws 大鼠中，肠道线虫 Nippostrongylus brosiliensis 感染诱导的肺肉芽肿反应受到抑制。”

山田 稔: "Nippostrongylus brasiliensis感染によって惹起される肺病変" 寄生虫学雑誌. 44(補). 86 (1995)

Minoru Yamada：“巴西圆线虫感染引起的肺部病变”，寄生虫学杂志 44（增刊）。

Arizono Naoki: "Lung granulomatous respones induced by infection with the intestinal nematocle Nippostrongylus brasiliensis is suppressed in mast cell-deficient Ws/Ws rats." Clinical and Experimental Immunalogy. 106. 55-61 (1996)

Arizono Naoki：“在肥大细胞缺陷的 Ws/Ws 大鼠中，肠道线虫感染引起的肺肉芽肿反应受到抑制。”

山田 稔: "Nippostrongylus brasiliensis感染によって惹起される肺病変" 寄生虫学雑誌. 44 (補). 86 (1995)

Minoru Yamada：“巴西圆线虫感染引起的肺部病变”，寄生虫学杂志 44（增刊）。