School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand.
Infect Immun. 2010 Feb;78(2):618-28. doi: 10.1128/IAI.00647-09. Epub 2009 Nov 23.
Schistosoma mansoni eggs produced by adult worms in the mesenteric vasculature become trapped in the liver, where they induce granulomatous lesions and strong immune responses. Infected individuals suffer from intestinal schistosomiasis (INT) in 90% of cases, whereas the remaining 10% present with severe hepatosplenic schistosomiasis (HS). The CBA/J mouse model mimics human disease, with 20% of infected mice developing hypersplenomegaly syndrome (HSS) that resembles HS and 80% developing moderate splenomegaly syndrome (MSS) similar to INT. We studied differential patterns of protein expression in livers of 20-week-infected CBA/J mice with MSS or HSS to understand the molecular changes that underlie these two disease forms. Using differential in-gel electrophoresis to identify differentially expressed protein spots, we found 80 protein spots significantly changed with infection and 35 changes specific to severe disease. In particular, the abundances of prohibitin 2, transferrin isoforms, and major urinary protein isoforms were significantly altered in HSS mice. Furthermore, annexin 5, glutathione S-transferase pi class, and S. mansoni phosphoenolpyruvate carboxykinase expression levels changed significantly with schistosome infection. Additionally, levels of major urinary protein decreased and levels of transferrin increased significantly in the sera of HSS mice compared to levels in sera of MSS or control mice, and these differences correlated to the degree of splenomegaly. These findings indicate that the liver protein abundances differ between MSS and HSS mice and may be used for the development of diagnostic markers for the early detection of hepatosplenic schistosomiasis.
曼氏血吸虫成虫在肠系膜血管中产生的虫卵会被困在肝脏中,在那里它们会引发肉芽肿病变和强烈的免疫反应。在受感染的个体中,90%会患肠道血吸虫病(INT),而其余 10%则会出现严重的肝脾血吸虫病(HS)。CBA/J 小鼠模型模拟了人类疾病,20%的感染小鼠会发展为类似于 HS 的脾肿大过度综合征(HSS),80%的感染小鼠会发展为类似于 INT 的中度脾肿大综合征(MSS)。我们研究了 MSS 或 HSS 感染的 20 周龄 CBA/J 小鼠肝脏中蛋白质表达的差异模式,以了解导致这两种疾病形式的分子变化。使用差异凝胶电泳来鉴定差异表达的蛋白质斑点,我们发现 80 个蛋白质斑点因感染而显著改变,其中 35 个变化与严重疾病有关。特别是在 HSS 小鼠中,抑制素 2、转铁蛋白同工型和主要尿蛋白同工型的丰度明显改变。此外, annexin 5、谷胱甘肽 S-转移酶 pi 类和 S. mansoni 磷酸烯醇丙酮酸羧激酶的表达水平随血吸虫感染而显著改变。此外,与 MSS 或对照小鼠相比,HSS 小鼠血清中的主要尿蛋白水平降低,转铁蛋白水平显著升高,这些差异与脾肿大程度相关。这些发现表明,MSS 和 HSS 小鼠肝脏的蛋白质丰度不同,可能用于开发诊断标志物以早期检测肝脾血吸虫病。