Cell-to-cell transfer of SAA1 protein in a cell culture model of systemic AA amyloidosis.
Cell-to-cell transfer of SAA1 protein in a cell culture model of systemic AA amyloidosis.
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DOI：
10.1038/srep45683
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发表时间：
2017-03-31
影响因子：
4.6
通讯作者：
Fändrich M
中科院分区：
文献类型：
--
作者：
Claus S;Puscalau-Girtu I;Walther P;Syrovets T;Simmet T;Haupt C;Fändrich M
系统性 AA 淀粉样变性是由血清淀粉样 A1 (SAA1) 蛋白的错误折叠和 AA 淀粉样原纤维在体内多个部位的沉积引起的。先前的研究已经证实，单核吞噬细胞对于体内沉积物的形成至关重要，并且将此类细胞的培养物暴露于 SAA1 蛋白会诱导培养皿内淀粉样蛋白沉积物的形成。在这项研究中，我们证明非纤维状和纤维状 SAA1 蛋白都可以在培养的 J774A.1 细胞（一种广泛使用的单核吞噬细胞模型）之间轻松转移。我们发现非原纤维 SAA1 蛋白的交换通常比原纤维更快。如果细胞被膜分开，交换就会被阻止，而增加细胞培养基的体积对观察到的交换效率只有很小的影响。结合扫描电子显微镜显示培养细胞之间存在各种类型的物理相互作用，我们得出结论，SAA1 蛋白的转移取决于细胞间的直接接触或隧道纳米管。
Systemic AA amyloidosis arises from the misfolding of serum amyloid A1 (SAA1) protein and the deposition of AA amyloid fibrils at multiple sites within the body. Previous research already established that mononuclear phagocytes are crucial for the formation of the deposits in vivo and exposure of cultures of such cells to SAA1 protein induces the formation of amyloid deposits within the culture dish. In this study we show that both non-fibrillar and fibrillar SAA1 protein can be readily transferred between cultured J774A.1 cells, a widely used model of mononuclear phagocytes. We find that the exchange is generally faster with non-fibrillar SAA1 protein than with fibrils. Exchange is blocked if cells are separated by a membrane, while increasing the volume of cell culture medium had only small effects on the observed exchange efficiency. Taken together with scanning electron microscopy showing the presence of the respective types of physical interactions between the cultured cells, we conclude that the transfer of SAA1 protein depends on direct cell-to-cell contacts or tunneling nanotubes.