Antibodies in the small intestine: mucosal synthesis and deposition of anti-glycosyl IgA, IgM, and IgG in the enterocyte brush border
Antibodies in the small intestine: mucosal synthesis and deposition of anti-glycosyl IgA, IgM, and IgG in the enterocyte brush border
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DOI：
10.1152/ajpgi.00021.2006
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发表时间：
2006-07-01
影响因子：
4.5
通讯作者：
Danielsen, E. Michael
中科院分区：
文献类型：
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作者：
Hansen, Gert H.;Niels-Christiansen, Lise-Lotte;Danielsen, E. Michael
对器官培养猪小肠黏膜外植体刷状缘免疫球蛋白的合成和沉积进行了研究。令人惊讶的是，在6小时的脉冲中合成了相当数量的IgM和IgA，在培养液和外植体中也检测到了新生成的抗体，包括微绒毛部分。对于IgA和IgM，这种亚细胞分布与由聚合免疫球蛋白受体介导的基底侧到根尖的跨细胞反应是一致的。Ig G是Fc受体FcRN的配基，β(2)-微球蛋白是FcRN的轻链，免疫金双标显示FcRN位于根尖下内体和肠细胞的基底外侧膜中。此外，还将β(2)-微球蛋白与G-琼脂糖凝胶上的免疫球蛋白进行共复性。根据荧光蛋白G的内化判断，除了少数分离的细胞外，不能检测到顶端的免疫球蛋白内吞作用。这表明，成人小肠中的免疫球蛋白主要是通过肠上皮细胞沿基底外侧至顶端方向运输的。所有与乳糖结合的免疫球蛋白中有很大一部分是凝集的，这表明针对共生肠道细菌产生的“抗糖基”抗体是在小肠局部合成的。因此，通过在刷子边缘部分沉积，这些抗体可能通过阻止凝集素样病原体进入刷子边缘表面而起到保护作用。
Synthesis and deposition of immunoglobulins in the brush border was studied in organ-cultured pig small intestinal mucosal explants. Surprisingly, comparable amounts of IgM and IgA were synthesized during a 6-h pulse, and also newly made IgG was detected in media and explants, including the microvillar fraction. For IgA and IgM, this subcellular distribution is consistent with basolateral-to-apical transcytosis, mediated by the polymeric immunoglobulin receptor. IgG is a ligand for the Fc receptor FcRn, and beta(2)-microglobulin, the light chain of FcRn, coclustered in immunogold double labeling with IgG in subapical endosomes and in the basolateral membrane of enterocytes. In addition, beta(2)-microglobulin was copurified with IgG on protein G-Sepharose. Apical endocytosis of IgG, as judged by internalization of fluorescent protein G, was not detectable except in a few isolated cells. This suggests that IgG in the adult small intestine is transported across the enterocyte mainly in the basolateral to apical direction. Significant fractions of all immunoglobulins bound to lactoseagarose, indicating that "anti-glycosyl" antibodies, raised against commensal gut bacteria, are synthesized locally in the small intestine. By partial deposition in the brush border, these antibodies therefore may have a protective function by preventing lectin-like pathogens from gaining access to the brush border surface.