Biophysical characteristics of anti-Galα1-3Gal IgM binding to cell surfaces:: Implications for xenotransplantation
Biophysical characteristics of anti-Galα1-3Gal IgM binding to cell surfaces:: Implications for xenotransplantation
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DOI：
10.1097/00007890-200102150-00018
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发表时间：
2001-02-15
期刊：
影响因子：
6.2
通讯作者：
Platt, JL
中科院分区：
文献类型：
--
作者：
Parker, W;Stitzenberg, KB;Platt, JL
背景针对细胞表面碳水化合物的天然抗体被认为对宿主防御和启动异种移植物和ABO不相容同种异体移植物的排斥至关重要。这些抗体与细胞表面结合和解离的生物物理性质尚未完全了解。我们研究了这些特性的Gal α 1 -3Gal抗体的结合猪内皮细胞表面，因为这种相互作用可能是相关的异种移植的临床应用。发现抗Gal α 1 -3Gal抗体与内皮细胞的初始结合速率取决于抗体浓度、抗体扩散和抗原浓度。完整糖萼的存在对抗体结合的影响大于抗原在细胞膜中的移动性。糖萼的破坏使平衡时结合的抗体量增加50%以上。尽管抗-Gal α 1 - 3 Gal抗体与细胞表面的结合可被可溶性Gal α 1 - 3 Gal抑制，但一旦结合，一些抗-Gal α 1 - 3 Gal不能被结合的竞争性抑制剂或通过用离液试剂变性结合的IG解离，但可以通过二硫键的还原解离，这表明与细胞表面的附着至少部分是，通过与表位的特异性反应以外的方式。
Background. Natural antibodies directed against cell surface carbohydrates are thought to be vital to host defense and to initiate the rejection of xenografts and ABO-incompatible allografts, The biophysical properties underlying the association and dissociation of these antibodies from cell surfaces is incompletely understood. We investigated those properties for the binding of Gal alpha1-3Gal antibodies to porcine endothelial cell surfaces, because such interactions might be relevant to the clinical application of xenotransplantation.Results and Conclusions. The initial rate of binding of anti-Gal alpha1-3Gal antibodies to endothelial cells was found to depend on antibody concentration, antibody diffusion, and antigen concentration, The presence of an intact glycocalyx had a greater impact on antibody binding than mobility of antigen in cell membranes, Disruption of glycocalyx increased the amount of antibody bound at equilibrium by more than 50%. Although the binding of anti-Gal alpha1-3Gal antibodies to cell surfaces could be inhibited by soluble Gal alpha1-3Gal, once bound, some anti-Gal alpha1-3Gal could not be dissociated by competitive inhibitors of binding or by denaturation of the bound Ig with chaotropic reagents, but could be dissociated by reduction of disulfide bonds, suggesting that attachment to cell surfaces was, at least in part, by means other than specific reaction with the epitope.