COMPLEMENT LYTIC ACTIVITY HAS NO ROLE IN THE PATHOGENESIS OF AUTOIMMUNE DIABETES IN NOD MICE
COMPLEMENT LYTIC ACTIVITY HAS NO ROLE IN THE PATHOGENESIS OF AUTOIMMUNE DIABETES IN NOD MICE
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DOI：
10.2337/diabetes.42.11.1574
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发表时间：
1993-11-01
期刊：
影响因子：
7.7
通讯作者：
COOKE, A
中科院分区：
文献类型：
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作者：
BAXTER, AG;COOKE, A
NOD小鼠被广泛用作器官特异性自身免疫模型，因为它对胰腺β细胞产生特异性自身免疫破坏。虽然很明显t细胞和单核细胞是破坏β细胞所必需的，但体液因子，如抗体和补体，也可能导致组织损伤。在实验模型中，试图通过移植胰岛的免疫隔离来治疗糖尿病，这就提出了保护胰岛免受补体级联中相对较小成分影响的需要。在本研究中，我们报道NOD小鼠没有补体溶解活性，在该模型中不需要排除补体。幼年NOD小鼠血清不能溶解包被兔抗体的羊红细胞。通过与C4缺失的CBA血清混合重建NOD血清的裂解活性，而不与C5缺失的DBA/2血清混合，表明NOD血清中存在C4，而不存在C5活性。用人C5在聚丙烯酰胺凝胶中电聚焦可以重建NOD血清的裂解活性。聚合酶链反应用于扩增DBA/2小鼠Hc（编码CS的基因）区域对应的基因组DNA片段，该区域携带导致这些小鼠缺乏C5蛋白表达的2碱基对缺失。来自多个菌落的DBA/2和NOD小鼠产生的片段2碱基比BALB/c小鼠中野生型等位基因产生的片段2碱基短。我们得出结论，NOD小鼠没有补体溶解活性，因为它们缺乏C5，因为Hc编码区有2个碱基对缺失，NOD小鼠不是测试在治疗糖尿病时是否需要免疫隔离室排除补体的合适模型。
The NOD mouse is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta-cells. Although it is clear that T-cells and monocytes are necessary for beta-cell destruction, humoral factors, such as antibodies and complement, may also contribute to tissue damage. Attempts to cure diabetes in experimental models by immunoisolation of transplanted islets has raised the need to protect the islets from the relatively small components of the complement cascade. In this study, we report that NOD mice have no complement lytic activity and that the exclusion of complement is unnecessary in this model. Sera from young NOD mice were unable to lyse sheep red blood cells coated with rabbit antibody. Lytic activity of NOD sera was reconstituted by mixing with C4-deficient CBA sera, but not C5-deficient DBA/2 sera, indicating the presence of C4, but the absence of C5 activity in NOD sera. Lytic activity of NOD sera could be reconstituted with human C5 electrofocused in polyacrylamide gel. The polymerase chain reaction was used to amplify fragments from genomic DNA corresponding to the region of Hc (the gene encoding CS) in DBA/2 mice, which carries a 2-base pair deletion responsible for the lack of C5 protein expression in these mice. DBA/2 and NOD mice from several colonies produced a fragment 2 bases shorter than that generated from the wild-type allele in BALB/c mice. We concluded that NOD mice have no complement lytic activity as they lack C5 because of a 2-base pair deletion in the coding region of Hc and that the NOD mouse is not an appropriate model to test the need for complement exclusion from immunoisolation chambers in the treatment of diabetes mellitus.