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

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

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