A primed state exists <i>in vivo</i> following histological regression of amyloidosis

Hawkins, Philip N.; Pepys, Mark B.

doi:10.1111/j.1365-2249.1990.tb03339.x

Cited by 32 publications

(17 citation statements)

References 7 publications

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“…That means the individuals may be primed for the amyloid disease in the case that a chronic inflammatory disease is acquired later. A similar primed state has been described in murine AA-amyloidosis after resolution of the deposits [57]. It will be very difficult to prove an association of ingestion of amyloid and development of AA-amyloidosis if this kind of delayed effect is true also in human.…”

Section: Possible Inoculation In Humansupporting

confidence: 52%

Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis

Westermark

2009

FEBS Letters

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a b s t r a c tSystemic AA-amyloidosis is a complication of chronic inflammatory diseases and the fibril protein AA derives from the acute phase reactant serum AA. AA-amyloidosis can be induced in mice by an inflammatory challenge. The lag phase before amyloid develops can be dramatically shortened by administration of a small amount of amyloid fibrils. Systemic AA-amyloidosis is transmissible in mice and may be so in humans. Since transmission can cross species barriers it is possible that AA-amyloidosis can be induced by amyloid in food, e.g. foie gras. In mice, development of AA-amyloidosis can also be accelerated by other components with amyloid-like properties. A new possible risk factor may appear with synthetically made fibrils from short peptides, constructed for tissue repair.

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Section: Possible Inoculation In Humansupporting

confidence: 52%

Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis

Westermark

2009

FEBS Letters

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“…Induction of murine AA amyloidosis by sustained chronic inflammation typically takes several weeks (7). However, mice in which AA amyloid deposits have regressed following remission of chronic inflammation are primed for rapid reaccumulation when they receive a new inflammatory stimulus (19), and previously untreated mice are readily primed by i.v. injection of amyloidotic tissue extracts or isolated amyloid fibrils, so-called amyloid enhancing factor (AEF) (20,21).…”

Section: Resultsmentioning

confidence: 99%

Pathogenetic mechanisms of amyloid A amyloidosis

Simons

Al‐Shawi

Ellmerich

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.

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“…Based on such findings, it was suggested that amyloid seeding potential is not solely based on primary structure, and that further study of the 3-D conformation of the protein is required [19]. More aggressive and severe forms of AA deposition were observed after the second inoculation, because the mice were primed after the first inoculation [7,22]. The maximal AA deposition was observed in mice receiving a second inoculation of murine AA fibrils, followed by bovine AA fibrils and lastly administration of silver nitrate alone.…”

Section: Discussionmentioning

confidence: 99%