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首页> 外文期刊>Protoplasma: An International Journal of Cell Biology >Localization of the human neonatal Fc receptor (FcRn) in human nasal epithelium
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Localization of the human neonatal Fc receptor (FcRn) in human nasal epithelium

机译：人新生儿Fc受体（FcRn）在人鼻上皮细胞中的定位

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摘要

The airway epithelium is a central player in the defense against pathogens including efficient mucociliary clearance and secretion of immunoglobulins, mainly polymeric IgA, but also IgG. Pulmonary administration of therapeutic antibodies on one hand, and intranasal immunization on the other, are powerful tools to treat airway infections. In either case, the airway epithelium is the primary site of antibody transfer. In various epithelia, bi-polar transcytosis of IgG and IgG immune complexes is mediated by the human neonatal Fc receptor, FcRn, but FcRn expression in the nasal epithelium had not been demonstrated, so far. We prepared affinity-purified antibodies against FcRn alpha-chain and confirmed their specificity by Western blotting and immunofluorescence microscopy. These antibodies were used to study the localization of FcRn alpha-chain in fixed nasal tissue. We here demonstrate for the first time that ciliated epithelial cells, basal cells, gland cells, and endothelial cells in the underlying connective tissue express the receptor. A predominant basolateral steady state distribution of the receptor was observed in ciliated epithelial as well as in gland cells. Co-localization of FcRn alpha-chain with IgG or with early sorting endosomes (EEA1-positive) but not with late endosomes/lysosomes (LAMP-2-positive) in ciliated cells was observed. This is indicative for the presence of the receptor in the recycling/transcytotic pathway but not in compartments involved in lysosomal degradation supporting the role of FcRn in IgG transcytosis in the nasal epithelium.
机译：气道上皮在抵御病原体（包括有效的粘膜纤毛清除和免疫球蛋白（主要是聚合IgA，但也包括IgG）的分泌）的防御中扮演着重要角色。一方面肺部给予治疗性抗体，另一方面进行鼻内免疫是治疗气道感染的有力工具。无论哪种情况，气道上皮都是抗体转移的主要部位。在各种上皮细胞中，IgG和IgG免疫复合物的双极转座作用是由人类新生儿Fc受体FcRn介导的，但迄今为止尚未证明FcRn在鼻上皮细胞中的表达。我们准备了针对FcRnα-链的亲和纯化抗体，并通过Western印迹和免疫荧光显微镜证实了其特异性。这些抗体用于研究FcRnα链在鼻腔固定组织中的定位。我们在这里首次证明纤毛上皮细胞，基底细胞，腺细胞和基础结缔组织中的内皮细胞表达受体。在纤毛上皮以及腺细胞中观察到受体的主要基底外侧稳态分布。在纤毛细胞中观察到FcRnα链与IgG或早期分选内体（EEA1阳性）共定位，而与晚期内体/溶酶体（LAMP-2阳性）共定位。这表明该受体存在于再循环/转胞吞途径中，但不存在于参与溶酶体降解的区室中，从而支持FcRn在鼻上皮中IgG转胞吞作用中的作用。

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