Role of Shiga toxin 2 (Stx2)-binding protein, human serum amyloid P component (HuSAP), in Shiga toxin-producing Escherichia coli infections:: assumption from in vitro and in vivo study using HuSAP and anti-Stx2 humanized monoclonal antibody TMA-15
Role of Shiga toxin 2 (Stx2)-binding protein, human serum amyloid P component (HuSAP), in Shiga toxin-producing Escherichia coli infections:: assumption from in vitro and in vivo study using HuSAP and anti-Stx2 humanized monoclonal antibody TMA-15
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DOI：
10.1016/s0006-291x(03)00901-x
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发表时间：
2003-06-13
影响因子：
3.1
通讯作者：
Matsumoto, Y
中科院分区：
文献类型：
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作者：
Kimura, T;Tani, S;Matsumoto, Y
志贺毒素2(Stx2)是产志贺毒素大肠杆菌(STEC)感染的主要致病因子。一些在体外中和Stx2的因子已经被证明存在于人血清中，我们最近确定它是人血清淀粉样蛋白P成分(HuSAP)。在这里，我们报告了HuSAP在STEC感染中的作用。HuSAP无法将Stx2挑战的小鼠从死亡中拯救出来，相反，当向小鼠注射较低剂量的TMA-15时，它反而降低了Stx2中和人源性单抗TMA-15的效果。相比之下，高剂量的TMA-15的疗效不受HuSAP的存在的影响。这些发现表明，HuSAP在人类循环中作为Stx2的载体蛋白，而不是Stx2中和因子，使用Stx2中和抗体(如TMA-15)进行被动免疫治疗有助于预防与STEC感染相关的严重并发症，即使在HuSAP存在的情况下也是如此。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Shiga toxin 2 (Stx2) is a major pathogenic factor in Shiga toxin-producing Escherichia coli (STEC) infections. Some factor that neutralizes Stx2 in vitro had been shown to be specifically present in human serum and we recently identified it as human serum amyloid P component (HuSAP). Here, we report the role of HuSAP in STEC infections. HuSAP could not rescue Stx2-challenged mice from death, and it instead reduced the efficacy of the Stx2-neutralizing humanized monoclonal antibody TMA-15 when a lower dose of TMA-15 was injected to the mice. By contrast, the efficacy of TMA-15 at a higher dose was uninfluenced by the presence of HuSAP. These findings suggest that HuSAP acts as a carrier protein of Stx2 rather than as a Stx2-neutralizing factor in the human circulation and that passive immune therapy with Stx2-neutralizing antibodies such as TMA-15 is useful to prevent severe complications associated with STEC infections even in the presence of HuSAP. (C) 2003 Elsevier Science (USA). All rights reserved.