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凝血因子VIII Fc融合蛋白而非FVIII通过FcγRIIa驱动人单核细胞衍生树突状细胞活化。

Factor VIII Fc Fusion Protein but not FVIII Drives Human Monocyte-Derived Dendritic Cell Activation via FcγRIIa.

作者信息

Kannicht Christoph, Danßmann Ilona, Weilandt Constanze, Derkow Katja, Kohla Guido, Geyer Henriette

机构信息

Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Walther-Nernst-Straße 3, 12489 Berlin, Germany.

出版信息

Hemasphere. 2020 Jan 3;4(1):e330. doi: 10.1097/HS9.0000000000000330. eCollection 2020 Feb.

DOI:10.1097/HS9.0000000000000330
PMID:32072146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7000470/
Abstract

This study compares the effect of recombinant Factor VIII Fc fusion protein (rFVIII-Fc) with recombinant FVIII (rFVIII) on monocyte-derived dendritic cells (moDC's). Cells treated with rFVIII-Fc showed morphological changes typical for cell activation, had a significant up-regulation of cell activation markers and produced higher levels of pro-inflammatory cytokines. Even after stimulation with Lipopolysaccharides, the addition of rFVIII-Fc led to increased expression of activation markers, indicating that rFVIII-Fc is capable of amplifying the maturation signal. On the contrary, cultivation of moDC's with rFVIII did not alter cell morphology or increase surface activation marker expression and pro-inflammatory cytokine production. The binding of the Fc domain to the activating Fcγ receptor IIa (FcγRIIa) can cause cell activation. Therefore, the effect of rFVIII-Fc on FcγRIIa was analyzed in detail. Cultivation of moDC's with rFVIII-Fc led to increased phosphorylation of FcγRIIa, which was not detected for rFVIII. Blocking FcγRIIa prior to the cultivation with rFVIII-Fc significantly reduced the activating effect of rFVIII-Fc, indicating that rFVIII-Fc-induced moDC activation was caused by FcγRIIa. Moreover, rFVIII-Fc bound to -transfected human embryonic kidney 293 cells. Taken together, our data present a new mechanism of moDC activation by rFVIII-Fc via FcγRIIa.

摘要

本研究比较了重组因子VIII Fc融合蛋白（rFVIII-Fc）与重组FVIII（rFVIII）对单核细胞来源的树突状细胞（moDC）的作用。用rFVIII-Fc处理的细胞表现出细胞活化典型的形态变化，细胞活化标志物显著上调，并产生更高水平的促炎细胞因子。即使在用脂多糖刺激后，添加rFVIII-Fc也会导致活化标志物表达增加，表明rFVIII-Fc能够放大成熟信号。相反，用rFVIII培养moDC不会改变细胞形态，也不会增加表面活化标志物表达和促炎细胞因子的产生。Fc结构域与活化性Fcγ受体IIa（FcγRIIa）的结合可导致细胞活化。因此，详细分析了rFVIII-Fc对FcγRIIa的作用。用rFVIII-Fc培养moDC会导致FcγRIIa磷酸化增加，而rFVIII未检测到这种情况。在用rFVIII-Fc培养之前阻断FcγRIIa可显著降低rFVIII-Fc的活化作用，表明rFVIII-Fc诱导的moDC活化是由FcγRIIa引起的。此外，rFVIII-Fc与转染的人胚肾293细胞结合。综上所述，我们的数据揭示了rFVIII-Fc通过FcγRIIa激活moDC的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/2f042a3b9e97/hs9-4-e330-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/47f4340e5700/hs9-4-e330-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/c8abc2f8472b/hs9-4-e330-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/477834f9f0a6/hs9-4-e330-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/2f042a3b9e97/hs9-4-e330-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/47f4340e5700/hs9-4-e330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/149890731c46/hs9-4-e330-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/6b73baef28ae/hs9-4-e330-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/f910dad23980/hs9-4-e330-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/a3afc56e409b/hs9-4-e330-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/1598d4e053eb/hs9-4-e330-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/c8abc2f8472b/hs9-4-e330-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/477834f9f0a6/hs9-4-e330-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f076/7000470/2f042a3b9e97/hs9-4-e330-g009.jpg

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2
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3
Tolerogenic properties of the Fc portion of IgG and its relevance to the treatment and management of hemophilia.
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Blood. 2018 May 17;131(20):2205-2214. doi: 10.1182/blood-2017-12-822908. Epub 2018 Mar 27.
4
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