Acceleration of Amyloid Protein A Amyloidosis by Amyloid-Like Synthetic Fibrils

Amyloid protein A (AA) amyloidosis is a consequence of some long-standing inflammatory conditions, and subsequently, an N-terminal fragment of the acute phase protein serum AA forms β -sheet fibrils that are deposited in different tissues. It is unknown why only some individuals develop AA amyloidos...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 5; pp. 2558 - 2563
Main Authors:	Johan, Katarzyna, Westermark, Gunilla, Engstrom, Ulla, Gustavsson, Asa, Hultman, Per, Westermark, Per
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences of the United States of America 03-03-1998 National Acad Sciences National Academy of Sciences The National Academy of Sciences
Subjects:	Amino Acid Sequence Amyloid plaque Amyloidosis Amyloidosis - chemically induced Amyloidosis - pathology Amyloidosis - physiopathology Amyloids Animals Antiserum Biological Sciences Disease Female Liver Lung - pathology Lung - ultrastructure Lungs Medical research MEDICIN MEDICINE Mice Mice, Inbred Strains Microscopy, Immunoelectron Molecular Sequence Data Peptide Fragments - chemical synthesis Peptide Fragments - chemistry Peptide Fragments - pharmacology Peptides Protein Structure, Secondary Proteins Radioactive decay Serum Amyloid A Protein - biosynthesis Serum Amyloid A Protein - chemistry Silver Solar fibrils Spleen
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Summary:	Amyloid protein A (AA) amyloidosis is a consequence of some long-standing inflammatory conditions, and subsequently, an N-terminal fragment of the acute phase protein serum AA forms β -sheet fibrils that are deposited in different tissues. It is unknown why only some individuals develop AA amyloidosis. In the mouse model, AA amyloidosis develops after ≈ 25 days of inflammatory challenge. This lag phase can be shortened dramatically by administration of a small amount of amyloid extract containing an as yet undefined amyloid-enhancing factor. In the present study, we show that preformed amyloid-like fibrils made from short synthetic peptides corresponding to parts of several different amyloid fibril proteins exert amyloidogenic enhancing activity when given i.v. to mice at the induction of inflammation. We followed i.v. administered, radiolabeled, heterologous, synthetic fibrils to the lung and to the perifollicular area in the spleen and found that new AA-amyloid fibrils developed on these preformed fibrils. Our findings thus show that preformed, synthetic, amyloid-like fibrils have an in vivo nidus activity and that amyloid-enhancing activity may occur, at least in part, through this mechanism. Our findings also show that fibrils of a heterologous chemical nature exert amyloid-enhancing activity.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Communicated by Donald F. Steiner, University of Chicago, Chicago, IL To whom reprint requests should be addressed. e-mail: perwe@pai.liu.se.
ISSN:	0027-8424 1091-6490 1091-6490
DOI:	10.1073/pnas.95.5.2558