Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.
Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.
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在聚合物免疫球蛋白受体/分泌成分缺陷的小鼠中，缺乏上皮免疫球蛋白A转运，粘膜泄漏增加。
DOI：
10.1084/jem.190.7.915
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发表时间：
1999-10-04
影响因子：
15.3
通讯作者：
Brandtzaeg, P
中科院分区：
文献类型：
--
作者：
Johansen, F E;Pekna, M;Norderhaug, I N;Haneberg, B;Hietala, M A;Krajci, P;Betsholtz, C;Brandtzaeg, P
粘液表面受到分泌型免疫球蛋白A（SIgA）和通过局部产生的二聚体伊加和五聚体IgM的外部易位产生的SIgM的特异性保护。它们的主动转运由上皮多聚IG受体（pIgR）介导，也称为跨膜分泌组分。全身和局部产生的抗体的细胞旁被动外部转移也提供粘膜保护，使得分泌免疫的生物学重要性难以评估。在这里，我们报告完全缺乏积极的外部伊加和IgM易位pIgR敲除小鼠，表明没有冗余的上皮转运机制。基因敲除小鼠的大小和生育能力正常，但血清IgG水平升高，包括大肠杆菌抗体，表明过度触发全身免疫。在缺乏SIgA（和SIgM）的情况下，其上皮屏障功能的恶化进一步证明了其唾液和粪便中白蛋白水平的升高，反映了血清蛋白的渗漏。因此，在这些实验动物的抗原暴露条件下，SIgA似乎对健康不是必需的。然而，我们的研究结果表明，SIgA有助于维持粘膜的稳态。因此，SIgA的产生可能是人类免疫病理学（如炎症性肠病或麸质敏感性肠病）启动的一个变量。
Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy.