Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors via a prion-like mechanism.
Recent studies clearly demonstrated that several types of pathogenic amyloid proteins acted as agents that could transmit amyloidosis by means of a prion-like mechanism. Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.
Tasaki
Masayoshi
M
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.
Ueda
Mitsuharu
M
Ochiai
Sho
S
Tanabe
Yuko
Y
Murata
Sho
S
Misumi
Yohei
Y
Su
Yu
Y
Sun
Xuguo
X
Shinriki
Satoru
S
Jono
Hirofumi
H
Shono
Makoto
M
Obayashi
Konen
K
Ando
Yukio
Y
D000686:Amyloidosis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D055354:Exosomes / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011328:Prions / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D006023:Glycoproteins; D011328:Prions; D000685:Serum Amyloid A Protein; C046748:amyloid enhancing factor