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. IL-5转基因小鼠（IL-5 Tg）蛛网膜下腔中的广州管圆线虫被大量嗜酸性粒细胞包围，嗜酸性粒细胞脱颗粒并将溶酶体物质排出到蠕虫上，导致蠕虫死亡。2.抗原特异性血清和脑脊液（CSF）伊加抗体检测感染后第5天和第7天向前，分别在IL-5 Tg和C3 H/HeN小鼠，虽然IL-5 Tg小鼠的抗体水平较高。3.抗CD 4抗体治疗干扰了BALB/c小鼠的杀虫作用，并改善了宿主的发病率，而抗CD 8抗体治疗未能改善发病率。4.肿瘤坏死因子-α不会导致感染小鼠发病。5.抗IL-5抗体治疗阻断蠕虫杀死，但未能改善宿主发病率。6.来自IL-5 Tg的嗜酸性粒细胞碱性粗蛋白在体外对20天的蠕虫具有蠕虫毒性。7.感染的C.B-17 +/+（+/+）和BALB/c nu/+（nu/+）均表现出较高的发病率， ...更多信息 而C.B-17 scid（SCID）和BALB/c nu/nu（nu/nu）均不能做到这一点。8. +/+、SCID和nu/nu小鼠的颅内蠕虫回收率明显高于nu/+和C57 BL/6小鼠。前三株，尤其是SCID和nu/nu，均未显示明显的CSF嗜酸性粒细胞增多。9. SCID和nu/nu小鼠均未能产生显著量的抗原特异性血清伊加和IgG1.10。先前用来自IL-5 Tg的腹膜嗜酸性粒细胞和来自感染的IL-5 Tg的血清伊加转移的感染的SCID小鼠产生与用嗜酸性粒细胞和正常血清转移的那些几乎相同的蠕虫恢复。这表明CSF中嗜酸性粒细胞的积聚发生在nu/nu中，而不是在SCID中。11。将未处理的IL-5 Tg和C3 H/HeN植入含有感染性第三期幼虫（L3）的扩散室（DC）中，在具有2 μ m滤膜的DC中发生细胞迁移，并且在IL-5 Tg中的迁移比在C3 H/HeN中更显著。L3幼虫在具有0.1 μ m滤膜的DC中比在具有2 μ m滤膜的DC中存活更好。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。”

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。”

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) ）

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)