Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.
Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.
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DOI：
10.1038/jid.2008.339
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发表时间：
2009-04
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影响因子：
--
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中科院分区：
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--
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桥粒体钙粘蛋白、桥粒蛋白和桥粒蛋白的细胞间相互作用是表皮细胞粘附所必需的。寻常型天疱疮（Pemphigus vulgaris， PV）是一种潜在致命的自身免疫性水疱疾病，其特征是抗粘连蛋白（Dsg） 3的自身抗体。在钙诱导的桥粒组装过程中，用PV患者产生的致病单价抗Dsg3单抗处理原代人角质形成细胞，可在2小时内导致细胞裂解物中不溶性部分的Dsg3和桥粒蛋白减少，但不导致桥粒蛋白（Dsc） 3减少。免疫荧光和抗体ELISA研究表明，致病性单抗引起细胞表面Dsg3的内化，而不是通过早期内体引起Dsc3的内化。电子显微镜显示，与非致病性单抗相比，致病性单抗处理的角质形成细胞缺乏结构良好的桥粒。相比之下，致病性单抗在24小时内引起预成型桥粒中Dsg3的迟发耗损，并对包括Dsc3和血小板红蛋白在内的多种桥粒蛋白产生影响。综上所述，这些研究表明致病性PV单抗在桥粒组装过程中特异性地引起新合成的Dsg3内化，从而与其致病活性相关。单价人PV抗dsg单抗再现了多克隆PV IgG对Dsg3的作用，这将有助于进一步研究天疱疮细胞粘附丧失的细胞机制。
The intercellular interactions of the desmosomal cadherins, desmoglein and desmocollin, are required for epidermal cell adhesion. Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by autoantibodies against desmoglein (Dsg) 3. During calcium-induced desmosome assembly, treatment of primary human keratinocytes with pathogenic monovalent anti-Dsg3 mAbs produced from a PV patient causes a decrease of Dsg3 and desmoplakin but not desmocollin (Dsc) 3 in the Triton-insoluble fraction of cell lysates within 2 hours. Immunofluorescence and antibody ELISA studies suggest that pathogenic mAbs cause internalization of cell surface Dsg3 but not Dsc3 via early endosomes. Electron microscopy demonstrated a lack of well-formed desmosomes in keratinocytes treated with pathogenic compared to nonpathogenic mAbs. In contrast, pathogenic mAbs caused late depletion of Dsg3 from preformed desmosomes at 24 hours, with effects on multiple desmosomal proteins including Dsc3 and plakoglobin. Together, these studies indicate that pathogenic PV mAbs specifically cause internalization of newly synthesized Dsg3 during desmosome assembly, correlating with their pathogenic activity. Monovalent human PV anti-Dsg mAbs reproduce the effects of polyclonal PV IgG on Dsg3 and will facilitate future studies to further dissect the cellular mechanisms for the loss of cell adhesion in pemphigus.
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影响因子：
4.8
作者：
Delva, Emmanuella;Jennings, Jean Marie;Kowalczyk, Andrew P.
通讯作者：
Kowalczyk, Andrew P.
DOI：
10.1016/s0190-9622(99)70183-0
发表时间：
1999-02-01
影响因子：
13.8
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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