Coeliac disease-specific autoantibodies targeted against transglutaminase 2 disturb angiogenesis
Coeliac disease-specific autoantibodies targeted against transglutaminase 2 disturb angiogenesis
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DOI：
10.1111/j.1365-2249.2008.03600.x
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发表时间：
2008-04-01
影响因子：
4.6
通讯作者：
Lindfors, K.
中科院分区：
文献类型：
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作者：
Myrsky, E.;Kaukinen, K.;Lindfors, K.
乳糜泻的特征在于针对转氨酶2（TG2）的免疫球蛋白A（伊加）类自身抗体，所述转氨酶2是一种也在血管生成中起作用的多功能蛋白。这些抗体存在于患者血清中，但也被发现与上皮基底膜下方和小肠粘膜中毛细血管周围的TG2结合。基于这些事实和信息，腹腔患者的粘膜血管的含麸质的饮食是混乱的，我们研究了腹腔疾病特异性自身抗体靶向TG2是否会干扰血管生成。腹腔疾病特异性自身抗体对体外血管生成的影响进行了研究，在血管生成细胞培养。记录了抗体与细胞的结合、内皮出芽、内皮和血管间充质细胞的迁移、两种细胞类型中肌动蛋白细胞骨架的完整性和血管间充质细胞的分化。在体外，伊加来源于腹腔疾病患者的含麸质的饮食结合到内皮细胞和血管间充质细胞的表面TG2，这种结合可以被抑制TG2的去除。此外，针对TG2的腹腔疾病特异性自身抗体干扰血管生成的几个步骤：内皮发芽和内皮细胞和血管间充质细胞的迁移。此外，自身抗体导致两种毛细血管细胞类型中肌动蛋白细胞骨架的解体，这最有可能是细胞迁移缺陷的原因。我们的结论是腹腔疾病特异性自身抗体识别TG2抑制血管生成在体外。这种血管生成过程的干扰可能导致在体内破坏的粘膜血管系统中看到的乳糜泻患者对含麸质的饮食。
Coeliac disease is characterized by immunoglobulin-A (IgA)-class autoantibodies targeted against transglutaminase 2 (TG2), a multi-functional protein also with a role in angiogenesis. These antibodies are present in patient serum but are also found bound to TG2 below the epithelial basement membrane and around capillaries in the small intestinal mucosa. Based on these facts and the information that the mucosal vasculature of coeliac patients on a gluten-containing diet is disorganized, we studied whether the coeliac disease-specific autoantibodies targeted against TG2 would disturb angiogenesis. The effects of coeliac disease-specific autoantibodies on in vitro angiogenesis were studied in angiogenic cell cultures. The binding of the antibodies to cells, endothelial sprouting, migration of both endothelial and vascular mesenchymal cells, the integrity of the actin cytoskeleton in both cell types and the differentiation of vascular mesenchymal cells were recorded. In vitro, IgA derived from coeliac disease patients on a gluten-containing diet binds to surface TG2 on endothelial and vascular mesenchymal cells and this binding can be inhibited by the removal of TG2. In addition, coeliac disease-specific autoantibodies targeting TG2 disturb several steps of angiogenesis: endothelial sprouting and the migration of both endothelial and vascular mesenchymal cells. Furthermore, the autoantibodies cause disorganization of the actin cytoskeleton in both capillary cell types that account most probably for the defective cellular migration. We conclude that coeliac disease-specific autoantibodies recognizing TG2 inhibit angiogenesis in vitro. This disturbance of the angiogenic process could lead in vivo to the disruption of the mucosal vasculature seen in coeliac disease patients on a gluten-containing diet.