Acceleration of murine AA amyloidosis by oral administration of amyloid fibrils extracted from different species

Abstract

We herein report that experimental murine amyloid A (AA) deposition is accelerated by oral administration of semipurified amyloid fibrils extracted from different species. Three groups of mice were treated with semipurified murine AA amyloid fibrils, semipurified bovine AA amyloid fibrils or semipurified human light chain-derived (A(lambda)) amyloid fibrils for 10 days. After 3 weeks, each mouse was subjected to inflammatory stimulation by subcutaneous injection with a mixture of complete Freund's adjuvant supplemented with Mycobacterium butyricum. The mice were killed on the third day after the inflammatory stimulation, and the spleen, liver, kidney and gastrointestinal tract were examined for amyloid deposits. Amyloid deposits were detected in 14 out of 15 mice treated with murine AA amyloid fibrils, 12 out of 15 mice treated with bovine AA amyloid fibrils and 11 out of 15 mice treated with human A(lambda) amyloid fibrils. No amyloid deposits were detected in control mice receiving the inflammatory stimulant alone or in amyloid fibril-treated mice without inflammatory stimulation. Our results suggest that AA amyloid deposition is accelerated by oral administration of semipurified amyloid fibrils when there is a concurrent inflammatory stimulation.

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

“…Prion-like transmission was also reported in mouse inflammation-associated amyloid A (AA) amyloidosis. 16,17 Many factors such as aging, primary sequence and mutation of amyloid proteins, genetic background of patients, as well as epigenetic factors, including inflammation, food composition and rearing conditions, may influence fibril formation and deposition in tissues. Transmission of amyloid fibrils from the environment may influence fibril formation as an important epigenetic factor.…”

Immunohistochemical distribution of Amyloid Deposits in 25 Cows Diagnosed with Systemic AA Amyloidosis

“…This sequence of reactions results in the systemic deposit of amyloid, mainly in the kidney, liver, spleen and intestine [7,12]. Recently, it has been reported that AA amyloidosis in mice is induced by the administration of amyloid enhancing factor (AEF), including AA amyloid fibrils, when there is concurrent inflammatory stimulation [4,11]. In cattle, there have been many reported cases of amyloidosis [5,6,8,[12][13][14][15].…”

“…C I L A g e ( y ) L i v e r S p l e e n K i d n e y H e a r t L u n g A d r e n a l g l a n d P a n c r e a s T h y r o i d g l a n d H y p o p h y s i s Recently, it has been reported that AA amyloidosis in mice is induced by the administration of AEF, including AA amyloid fibrils, when there is concurrent inflammatory stimulation [4,11]. Fibrillogenesis of AA amyloid occurs in a two-stage or biphasic process [4,16]. The first phase involves the synthesis of precursor proteins that accumulate in sufficient quantities to initiate an amyloid deposit.…”

“…This phase, known as the preamyloid phase, continues for a period ranging from several days to several years without an actual amyloid deposit. The duration of the preamyloid phase depends on the inflammatory stimuli and the level of SAA [4]. The second phase, called the amyloid phase, is thought to result from the generation of a nidus or fibrillar network onto which amyloid can be deposited [4].…”

“…The duration of the preamyloid phase depends on the inflammatory stimuli and the level of SAA [4]. The second phase, called the amyloid phase, is thought to result from the generation of a nidus or fibrillar network onto which amyloid can be deposited [4]. The preamyloid phase of experimentally induced murine AA amyloidosis can be greatly shortened in recipient animals when AEF is administered by intravenous or intraperitoneal injection, or by ingestion concomitant with an inflammatory episode [1,7].…”