Studies on helminthotoxicity and host morbidity by eosinophils from IL-5 transgenic mice in Angiostrongylus cantonensis infection

IL-5转基因小鼠嗜酸性粒细胞对广州管圆线虫感染的蠕虫毒性和宿主发病率的研究

• 批准号: 08670274
• 负责人: YOSHIMURA Kentaro
• 金额: $ 1.6万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670274/
• 关键词: Angiostrongylus cantonensis; eosinophil; IL-5 transgenic mice; C.B-17 scid; BALB; c nu; nu; diffusion chamber; IgA; CD4^+T cell; 広東住血線虫; IL-5 transgenic mouse; C.B.-17 scid; diffusion chamber; CD8^+T細胞; 髄液; major basic protein; eosinophil

This study demonstrated : 1. Angiostrongylus cantonensis worms in the subarachnoid spaces of IL-5 transgenic mice (IL-5 Tg) were surrounded by numerous eosinophils which degranulated and discharged lysosomal materials on to the worms, leading to worm killing. 2. Antigen-specific serum and cerebrospinal fluid (CSF) IgA antibodies were detectable on days 5 and 7 postinfection onward, respectively, in both IL-5 Tg and C3H/HeN mice, although the antibody level was higher in IL-5 Tg mice. 3. Anti-CD4 antibody treatment interfered with worm killing in BALB/c mice and improved host morbidity, whereas anti-CD8 antibody treatment failed to improve the morbidity. 4. Tumor necrosis factor-alpha does not cause morbidity of infected mice. 5. Anti-IL-5 antibody treatment blocked worm killing but failed to improve host morbidity. 6. Crude eosinophil basic proteins from IL-5 Tg was helminthotoxic to day 20 worms in vitro. 7. Both infected C.B-17 +/+ (+/+) and BALB/c nu/+ (nu/+) showed high morbidity, … More while both C.B-17 scid (SCID) and BALB/c nu/nu (nu/nu) failed to do so. 8. Intracranial worm recovery was markedly higher in +/+, SCID and nu/nu mice than in nu/+ and C57BL/6 mice. The former three strains, especially SCID and nu/nu, failed to show significant CSF eosinophilia. 9. Both SCID and nu/nu mice failed to produce a significant amount of antigen specific serum IgA and IgG1.10. Infected SCID mice previously transferred with peritoneal eosinophils from IL-5 Tg and also with serum IgA from infected IL-5 Tg yielded almost the same worm recovery as those transferred with eosinophils and the normal serum. This indicated that the accumulation of eosinophils in CSF occurs in nu/nu but not in SCID.11. When naive IL-5 Tg and C3H/HeN were implanted with a diffusion chamber (DC) containing infective third stage larvae (L3), cellular migration occurred in a DC with 2mum filter membrane, and the migration was more prominent in IL-5 Tg than in C3H/HeN.L3 larvae survived better in a DC with 0.1mum filter membrane than in a DC with 2mum membrane. Less

本研究表明：1.在IL-5转基因小鼠(IL-5TG)蛛网膜下腔内，广州管圆线虫被大量的嗜酸性粒细胞包围，这些嗜酸性粒细胞脱颗粒并将溶酶体物质释放到虫体上，导致虫体死亡。2.IL-5TG和C3H/HEN小鼠在感染后第5天和第7天均可检测到抗原特异性的血清和脑脊液IgA抗体，但IL-5 TG小鼠的抗体水平较高。3.抗CD4抗体治疗干扰了BALB/c小鼠的杀虫作用，提高了宿主发病率，而抗CD8抗体治疗不能改善宿主发病率。4.肿瘤坏死因子-α对感染小鼠无致病作用。5.抗IL-5抗体治疗阻止了杀虫作用，但不能改善宿主发病率。6.IL-5TG的嗜酸性粒细胞碱性蛋白粗提物对20日龄幼虫有明显的体外杀虫作用。7.感染的C.B-17+/+(+/+)和BALB/c nu/+(nu/+)的发病率都很高，…而C.B-17 SCID(SCID)和BALB/c nu/nu(nu/nu)都未能做到这一点。8.+/+、SCID和nu/nu小鼠的颅内蠕虫恢复率显著高于nu/+和C57BL/6小鼠。前三株，尤其是SCID和nu/nu，未表现出明显的脑脊液嗜酸性。9.SCID和nu/nu小鼠均不能产生大量的抗原特异性血清IgA和IgG1.10。感染的SCID小鼠在接种IL-5 TG来源的嗜酸性粒细胞和感染IL-5 TG来源的血清IgA后，虫体回收率与转入嗜酸性粒细胞和正常血清的几乎相同。这表明嗜酸性粒细胞在脑脊液中的聚集发生在nu/nu而不是在SCID中。将幼虫IL-5TG和C3H/HEN植入含有感染性第三期幼虫(L3)的扩散腔(DC)后，细胞在有2um滤膜的DC中发生迁移，且IL-5TG的迁移比C3H/HeN中的迁移更明显。较少

项目成果

Yoshimura, K.: "Angiostrongylus (Parastrongylus)and less common nematodes." Cox FEG,Kreier JP,Wakelin D (eds) Topley & Wilson's Microbiology and Microbial Infections. 9th edn.Vol.5. Parasitology, Arnold, London. 635-659 (1998)

Yoshimura, K.：“管圆线虫（副圆线虫）和不太常见的线虫。”

Sugaya,H.: "Mediastinal lymph node cells of Angiostrongylus cantonensis-infected rats respond to antigens and release interleukin 5 in vitro." International Journal for Parasitology. 26. 543-551 (1996)

Sugaya, H.：“感染广州管圆线虫的大鼠的纵隔淋巴结细胞对抗原做出反应并在体外释放白细胞介素 5。”

Yosimura, K.: "Cox FEG,Kreier JP,Wakelin D(eds)Topley & Wilson‘s Microbiology and Microbial Infections.9th edn.Vol.5.Parasitology,Arnold,London" Angiostrongylus(Parastrongylus)and less common nematodes, 25 (1998)

Yosimura, K.：“Cox FEG，Kreier JP，Wakelin D（编辑）Topley & Wilsons Microbiology and Microbial Infections.9th edn.Vol.5.Parasitology，Arnold，London” 管圆线虫（副圆线虫）和不太常见的线虫，25 (1998) ）

Yoshimura, K.: "Eosinophils intravenously transferred into Angiostrongylus cantonensis infected nude mice Kill intracranial worms in vivo." Acta Parasitol Turcica. Suppl 1. 281-291 (1996)

Yoshimura, K.：“将嗜酸性粒细胞静脉注射到感染广州管圆线虫的裸鼠体内，杀死体内的颅内蠕虫。”

Yoshida,T.: "Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5 R α-deficient mice." Immunity. 4. 483-494 (1996)

Yoshida, T.：“IL-5 R α 缺陷小鼠的 B-1 细胞发育缺陷和对广州管圆线虫的免疫力受损。” 4. 483-494 (1996)