LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation
LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation
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DOI：
10.1093/glycob/cwj058
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发表时间：
2006-03-01
期刊：
影响因子：
4.3
通讯作者：
Hokke, CH
中科院分区：
文献类型：
--
作者：
Van de Vijver, KK;Deelder, AM;Hokke, CH
血吸虫是主要的寄生蠕虫，表达大量的糖结合物，在受感染的人类宿主中激发体液和细胞免疫反应。血吸虫病的主要病理是由于组织诱捕卵周围肉芽肿的形成和由此导致的器官损伤。用抗原包被珠肝植入诱导小鼠肉芽肿模型，确定血吸虫可溶性虫卵抗原(SEA)的多糖部分启动了肉芽肿的发生。为了确定这个复杂的海洋混合物中哪些单独的糖链是致粒的，我们在同一小鼠模型中测试了各种血吸虫卵特有的合成寡糖的结合物，包括GalNAc beta 1-4GlcNAc(LacdiNAc，LDN)、GalBeta 1-4(Fuc Alpha 1-3)GlcNAc(Lewis(X))、Fuc Alpha 1-2Fuc Alpha 1-3GlcNAc(DF-Gn)和Fuc Alpha 1-3GalNAc Beta 1-4(Fuc Alpha 1-3)GlcNAc(F-LDN-F)。核糖核酸酶(RNase)A和B以及不同的胎球蛋白糖型作为对照。只有携带与末端LacdiNAc或Galβ1-4GlcNAc(LacNAc，LN)元件的糖偶联物的珠子才会引起肉芽肿，其巨噬细胞、淋巴细胞和嗜酸性粒细胞水平与血吸虫卵在自然感染中引起的肉芽肿病变相似。未包被的珠子和包被岩藻糖化的糖结合物或缺少末端暴露的半乳糖或半乳糖的糖结合物的小球，只吸引单层巨噬细胞。这些结果表明，肝肉芽肿的形成是由携带末端LacNAc或LacdiNAc的糖偶联物特异性地触发的，这两种成分都是血吸虫卵的成分。
Schistosomes, major parasitic helminths, express numerous glycoconjugates that provoke humoral and cellular immune responses in the infected human host. The main pathology in schistosomiasis is due to the formation of granulomas around tissue-trapped eggs and the resulting organ damage. By using a mouse model of induction of granulomas by hepatic implantation of antigen-coated beads, it has been determined that the glycan part of schistosomal soluble egg antigens (SEA) initiates granulomogenesis. To identify which individual glycan elements in this complex SEA mixture are granulomogenic, we have tested in the same mouse model conjugates of various synthetic oligosaccharides characteristic for schistosome eggs, including GalNAc beta 1-4GlcNAc (LacdiNAc, LDN), Gal beta 1-4(Fuc alpha 1-3)GlcNAc (Lewis(x)), Fuc alpha 1-2Fuc alpha 1-3GlcNAc (DF-Gn), and Fuc alpha 1-3GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc (F-LDN-F). Ribonuclease (RNase) A and B, and different fetuin glycoforms were included as controls. Only beads that carry glycoconjugates with terminal LacdiNAc or Gal beta 1-4GlcNAc (LacNAc, LN) elements gave rise to granulomas, with macrophage, lymphocyte, and eosinophil levels similar to the granulomatous lesions caused by schistosome eggs in a natural infection. Uncoated beads, and beads coated with fucosylated glycoconjugates or glycoconjugates lacking terminally exposed Gal or GalNAc, only attracted a monolayer of macrophages. These results indicate that the formation of hepatic granulomas is triggered specifically by glycoconjugates which carry terminal LacNAc or LacdiNAc, both constituents of the schistosome egg.