Angiogenic activity of an Onchocerca volvulus Ancylostoma secreted protein homologue
Angiogenic activity of an Onchocerca volvulus Ancylostoma secreted protein homologue
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DOI：
10.1016/s0166-6851(03)00094-x
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发表时间：
2003-06-01
影响因子：
1.5
通讯作者：
Unnasch, TR
中科院分区：
文献类型：
--
作者：
Higazi, TB;Pearlman, E;Unnasch, TR
血管生成是眼盘尾丝虫病发展的重要步骤。在之前的研究中，已经证明钩虫分泌蛋白家族的盘尾丝虫同源物具有显着的血管生成活性。当前研究的总体目标是确定这种血管生成效应是通过直接还是间接机制发挥的。这些研究集中于该家族的一个成员 OvASP-2，因为这种蛋白质在微丝蚴中表达，微丝蚴是引起眼盘尾丝虫病的寄生虫阶段。编码截短和全长开放阅读框的克隆与大肠杆菌麦芽糖结合蛋白（MBP）表达为融合蛋白，并在体外和体内与单独的MBP进行血管生成活性比较。仅表达 OvASP-2 前 105 个氨基酸的截短构建体在诱导新血管形成方面与全长蛋白一样活跃。全长融合蛋白在体外不刺激血管内皮细胞增殖或产生血管内皮生长因子，表明OvASP-2不直接刺激血管生成。序列分析表明编码OvASP-2的基因含有5个内含子。对西非盘旋丝虫致盲和非致盲菌株的基因组位点的序列比较表明，所测试的各种分离株之间存在一些多态性。然而，这些多态性均不能用于区分寄生虫菌株，这表明 OvASP-2 的定性变异无法解释两种寄生虫菌株眼部致病潜力的差异。 (C) 2003 Elsevier Science B.V. 保留所有权利。
Angiogenesis is an important step in the development of ocular onchocercaisis. In previous studies, it has been demonstrated that Onchocerca volvidus homologues of the Ancylostoma secreted protein family have pronounced angiogenic activity. The overall goal of the current study was to determine if this angiogenic effect is exerted through a direct or indirect mechanism. These studies focused on one member of this family, OvASP-2, as this protein is expressed in microfilaria, the stage of the parasite that causes ocular onchocercaisis. Clones encoding truncated and full length open reading frames were expressed as fusion proteins with Escherichia coli maltose binding protein (MBP), and angiogenic activity was compared in vitro and in vivo with MBP alone. Truncated constructs expressing only the first 105 amino acids of OvASP-2 were as active as the full length protein in inducing new blood vessel formation. The full length fusion protein did not stimulate proliferation or production of vascular endothelial growth factor in vascular endothelial cells in vitro, indicating that OvASP-2 does not directly stimulate angiogenesis. Sequence analysis demonstrated that the gene encoding OvASP-2 contained five introns. Sequence comparisons of the genomic loci from West African blinding and non-blinding strains of O. volvulus revealed that some polymorphism existed among the various isolates tested. However, none of these polymorphisms could be used to differentiate the parasite strains, suggesting that qualitative variation in OvASP-2 could not explain the difference in ocular pathogenic potential of the two parasite strains. (C) 2003 Elsevier Science B.V. All rights reserved.