Abstract
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.
Highlights
AA amyloidosis is a classical form of systemic amyloidosis that involves amyloid deposits in multiple organs[1]
serum amyloid A1 (SAA1) fibrils refer to samples of aged recombinant SAA1 protein that bind the amyloid-binding dyes Thioflavin T (ThT; Fig. 1a) and Congo red (CR; Fig. 1b) and contain SAA1 protein that can quantitatively be pelleted by centrifugation for 30 min at 16,000 g (Fig. 1c)
In this study we show that SAA1 protein can be efficiently transferred between cultured J774A.1 cells that were loaded with different fluorescent variants of SAA1 protein
Summary
AA amyloidosis is a classical form of systemic amyloidosis that involves amyloid deposits in multiple organs[1]. Exposure of cultures of primary monocytes, macrophages or monocytic cell lines to acute-phase levels of SAA1 protein in the medium leads to the formation of amyloid deposits within the culture dish and has given rise to a facile cell culture model for studying the process of cellular amyloid biogenesis[17,18]. In this study it is used to address the question of a possible cell-to-cell transfer of soluble SAA1 protein and SAA1 fibrils This issue has so far been analysed for several neurodegenerative amyloid diseases where the transfer of amyloid proteins or aggregates is thought to underlie the spreading of disease inside the brain[24]. In this study we address this issue and analysed the possible transfer of SAA1 fibrils and non-fibrillar SAA1 protein in the cell culture model of systemic AA amyloidosis
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