Composition of the lectin pathway of complement in Gallus gallus:: Absence of mannan-binding lectin-associated serine protease-1 in birds

Composition of the lectin pathway of complement in Gallus gallus:: Absence of mannan-binding lectin-associated serine protease-1 in birds
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DOI:
10.4049/jimmunol.174.8.4998
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发表时间:
2005-04-15
影响因子:
4.4
通讯作者:
Schwaeble, WJ
Schwaeble, WJ
中科院分区:
医学2区
文献类型:
--
作者:
Lynch, NJ;Khan, SUH;Schwaeble, WJ

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补体的凝集素途径被识别并结合微生物多糖的多分子复合物激活。这些复合物包含多聚体碳水化合物识别亚基(甘露聚糖结合凝集素(MBL)或纤维胶凝蛋白)、三种MBL相关丝氨酸蛋白酶(MASP-1、MASP-2和MASP-3)和MAp 19(MASP-2基因的截短产物)。在这项研究中,我们报告了鸡MASP-2、MASP-3和MAp 19的克隆及其基因的组织,以及鸡MBL和一种新的纤维胶凝蛋白的基因的组织。哺乳动物通常拥有两个MBL基因和两个或三个纤维胶凝蛋白基因,但鸡只有一个,这两个基因都代表了哺乳动物基因的单一祖先。鸡MASP-2的一级结构与人和小鼠MASP-2的一级结构具有54%的同一性,并且其基因的组织与哺乳动物中的相同。MASP-3甚至更保守;鸡MASP-3与人和非洲爪蟾MASP-3共享类似于其75%的残基。它比其他凝集素途径组分更广泛地表达,表明MASP-3的可能功能不同于其他组分的功能。在哺乳动物中,MASP-1和MASP-3是单一结构基因的选择性剪接产物。我们证明了MASP-1在鸟类中的缺失,这可能是由在胚胎发育期间MASP-1特异性外显子的丢失引起的。尽管在鸡和其他鸟类的血清中缺乏MASP-1样酶活性,但禽类凝集素途径复合物有效地激活C4。
The lectin pathway of complement is activated by multimolecular complexes that recognize and bind to microbial polysaccharides. These complexes comprise a multimeric carbohydrate recognition subunit (either mannan-binding lectin (MBL) or a ficolin), three MBL-associated serine proteases (MASP-1, -2, and -3), and MAp19 (a truncated product of the MASP-2 gene). In this study we report the cloning of chicken MASP-2, MASP-3, and MAp19 and the organization of their genes and those for chicken MBL and a novel ficolin. Mammals usually possess two MBL genes and two or three ficolin genes, but chickens have only one of each, both of which represent the undiversified ancestors of the mammalian genes. The primary structure of chicken MASP-2 is 54 % identical with those of the human and mouse MASP-2, and the organization of its gene is the same as in mammals. MASP-3 is even more conserved; chicken MASP-3 shares similar to 75 % of its residues with human and Xenopus MASP-3. It is more widely expressed than other lectin pathway components, suggesting a possible function of MASP-3 different from those of the other components. In mammals, MASP-1 and MASP-3 are alternatively spliced products of a single structural gene. We demonstrate the absence of MASP-1 in birds, possibly caused by the loss of MASP-1-specific exons during phylogeny. Despite the lack of MASP-1-like enzymatic activity in sera of chicken and other birds, avian lectin pathway complexes efficiently activate C4.