Mannose-binding lectin deficiency - revisited
Mannose-binding lectin deficiency - revisited
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DOI：
10.1016/s0161-5890(03)00104-4
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发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Koch, C
中科院分区：
文献类型：
--
作者：
Garred, P;Larsen, F;Koch, C
由于甘露糖结合凝集素 (MBL) 在先天免疫中的作用，人们对它越来越感兴趣。在这项调查中，我们提供了新旧数据的混合，描述了 MBL 多态性可能对分子水平和功能产生的影响。mbl2 基因外显子 1 中的三个单核苷酸取代导致循环中功能性 MBL 显着减少。此外，启动子变异会影响 MBL 的表达。据推测，结构变异等位基因可能会破坏MBL三聚体的组装或加速蛋白质的降解，从而导致MBL血清浓度降低。我们使用相同的抗体捕获和检测MBL，在双夹心抗体ELISA中分析了1183种不同的血清，并发现与先前提出的结果相同的结果，表明不同的MBL启动子等位基因对MBL的影响具有深远的影响。 MBL 血清浓度。然而，新的抗 MBL 单克隆抗体的使用表明，循环中 MBL 的量对结构变异等位基因的存在的依赖程度比以前预期的要小。 MBL 的分子特征表明，来自正常 MBL 基因型纯合子的供体的血清主要含有高分子量 MBL，而来自变异等位基因杂合子的个体的血清则含有高分子量 MBL。 和低分子量MBL。高分子量和低分子量 MBL 之间的比率取决于正常单倍型上的 MBL 启动子类型。源自 MBL 变异等位基因纯合个体的血清主要含有低分子量 MBL。在 MBL 的不同寡聚物中，只有高分子量形式能够有效结合甘露聚糖并激活补体。与之前的概念相反，我们证明变异等位基因在循环中产生相对较高水平的 MBL。然而，与正常 MBL 相比，变异 MBL 的分子量较低并且功能失调。变异 MBL 的生理相关性仍有待确定。 (C) 2003 Elsevier Ltd. 保留所有权利。
There is an emerging interest for mannose-binding lectin (MBL) due to its role in innate immunity. In this survey we present a mixture of old and new data describing the effect MBL polymorphisms may have on the level and function of the molecule.Three single nucleotide substitutions in exon 1 of the mbl2 gene cause a dominant decrease of functional MBL in the circulation. Additionally, promoter variants influence expression of MBL. It has been assumed that the structural variant alleles may disrupt the assembly of MBL trimers or accelerate the degradation of the protein, thereby causing the decrease in MBL serum concentrations.We have analysed 1183 different sera in a double sandwich antibody ELISA using the same antibody to capture and detect MBL and find the same results as have been presented previously showing that different MBL promoter alleles have profound effect of on the MBL serum concentration. The use of a new anti-MBL monoclonal antibody, however, has shown that the amount of MBL in the circulation is less dependent on the presence of structural variant alleles than previously anticipated.Molecular characterisation of MBL revealed that sera from donors homozygous for the normal MBL genotype predominantly contained high molecular weight MBL, while sera from individuals heterozygous for the variant alleles contained both high and low molecular weight MBL. The ratio between high and low molecular weight MBL was dependent on the MBL promoter type on the normal haplotype. Sera deriving from individuals homozygous for MBL variant alleles contained mainly low molecular weight MBL. Of the different oligomers of MBL only the high molecular weight forms bound mannan efficiently and activated complement.In contrast to a previous notion, we demonstrate that variant alleles give rise to relatively high levels of MBL in the circulation. However, the variant MBL has lower molecular weight and is dysfunctional compared to normal MBL. The physiological relevance of variant MBL remains to be established. (C) 2003 Elsevier Ltd. All rights reserved.