Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis
Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis
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DOI：
10.1016/s1286-4579(02)01597-6
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发表时间：
2002-07-01
影响因子：
5.8
通讯作者：
Ezekowitz, RAB
中科院分区：
文献类型：
--
作者：
Takahashi, K;Gordon, J;Ezekowitz, RAB
甘露糖结合凝集素（MBL）（也称为甘露糖结合蛋白）是一种血清蛋白，在先天免疫中起“抗抗体”作用。在人类中，MBL由单个基因编码，而在小鼠中有两种同源蛋白，MBL-A和MBL-C。为了评估这两种形式的MBL的相对作用，我们创建了MBL-C足够的MBL-A无效小鼠。我们发现MBL-A基因敲除小鼠在脓毒性腹膜炎模型中24 h、48 h和10 d的存活率高于野生型小鼠和补体3基因敲除小鼠（P < 0.05）。用人MBL重建这些小鼠逆转了表型。存活小鼠血液和腹腔中TNF-α和IL-6水平显著降低（P < 0.01）。体外研究表明，与使用野生型血清的细菌相比，使用MBL-A缺陷血清调理的细菌通过腹腔巨噬细胞诱导的细胞因子显着减少。我们的研究结果表明，MBL-A是在体内和体外的小鼠炎症的调节剂，MBL的作用可能超出其作为调理素的作用。(C)2002年，Elsevier SAS科学与医学版。All rights reserved.
The mannose-binding lectin (MBL) (also known as the mannose-binding protein) is a serum protein that plays a role as an "ante-antibody" in innate immunity. In man, MBL is encoded by a single gene, whereas in mice there are two homologous proteins, MBL-A and MBL-C. In order to evaluate the relative roles of these two forms of MBL, we created MBL-A null mice that were MBL-C sufficient. We found MBL-A null mice had enhanced survival in a septic peritonitis model compared to wild-type mice and complement 3 null mice at 24 h, 48 h and 10 d (P < 0.05). Reconstitution of these mice with human MBL reversed the phenotype. Surviving mice had significantly decreased TNF-α and IL-6 levels in the blood and peritoneal cavity (P < 0.01). In vitro studies indicate that bacteria opsonized with MBL-A-deficient serum induced significantly less cytokine by peritoneal macrophages compared to those with wild-type serum. Our results indicate that MBL-A is a modulator of inflammation in vivo and in vitro in the mouse and that the role of MBL may extend beyond its role as an opsonin. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.