The new basement membrane antigen recognized by the monoclonal antibody GB3 is a large size glycoprotein: modulation of its expression by retinoic acid.
The new basement membrane antigen recognized by the monoclonal antibody GB3 is a large size glycoprotein: modulation of its expression by retinoic acid.
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单克隆抗体 GB3 识别的新基底膜抗原是一种大尺寸糖蛋白：通过视黄酸调节其表达。
DOI：
10.1016/0005-2736(88)90273-8
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
J. Ortonne
中科院分区：
文献类型：
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作者：
P. Verrando;A;J. Ortonne
本研究对单克隆抗体GB3识别的半胱胺酮相关表皮基底膜成分进行了进一步的生化研究。我们以前发现这种成分的表达在一种称为致死性大疱性结缔组织松解的严重遗传性皮肤病中受损。我们现在证明该因子是一个非常大的糖蛋白（表观分子量，600 kDa），由93.5至150 kDa范围内的多肽组成，并含有n -连接的低聚糖链。对培养的人角质形成细胞的GB3放射免疫沉淀肽进行了内do-β- n -乙酰氨基葡萄糖苷酶和神经氨酸酶水解以及豆豆蛋白A的结合实验。他们发现抗原亚基可能同时携带“高甘露糖”和“复杂”型糖苷链。培养的人角质形成细胞长期暴露于视黄酸（10−8至10−6M）中，这些糖苷链的总体体积没有明显变化，但观察到抗原的合成和分泌呈剂量依赖性增加。在10t-6M维甲酸处理的培养基中，相对诱导因子为4。这种诱导作用也通过间接免疫荧光在基底膜区从培养的人角质细胞上观察到，这些细胞生长在死亡的去表皮化的真皮上。这些结果进一步强调了糖蛋白对细胞-细胞和细胞-基质附着的影响。此外，调节这种抗原的能力必须与理解致死性大疱性结界表皮松解的分子缺陷有关。
Further biochemical investigations on the hemidesmosone-associated epidermal basement membrane component recognized by the monoclonal antibody GB3 are presented in this study. We previously found that the expression of this constituent is impaired in a severe genedermatosis termed lethal junctional epidermolysis bullosa. We demonstrate now that this factor is a very large glycoprotein (apparent molecular weight, 600 kDa) made up of polypeptides in the range of 93.5 to 150 kDa, and containing N-linked oligosaccharide chains. Both endo-β-N-acetylglucosaminidases and neuraminidase hydrolysis, as well as concanavalin A binding experiments were performed on the GB3 radioimmunoprecipitated peptides from cultured human keratinocytes. They showed that the antigen subunits probably bear both ‘high-mannose’ and ‘complex’ type glycosidic chains. The chronic exposure of cultured human keratinocytes to retinoic acid (10−8to 10−6M) resulted in no apparent changes in the overall bulk of these glycosidic chains, but a dose-dependent increase of synthesis and secretion of the antigen was observed. A relative induction factor of 4 was obtained in cultures treated with 10t-6M retinoic acid. This induction was also observed morphologically by indirect immunofluorescence at the basement membrane zone from cultured human keratinocytes grown on dead de-epidermized dermis. These results further emphasize the influence of glycoprotiens in cell-cell and cell-substratum attachment. Furthermore, the ability to modulate this antigen must be relevant for the understanding of the molecular defect involved in lethal junctional epidermolysis bullosa.