Alveolar hydatid cyst (AHC): inflammation-induced reactive gastrointestinal (GL) amyloidosis in AHC-infected mice and chemical characterization of the GL amyloid.
A high incidence of GI amyloidosis has been described in patients with various forms of systemic amyloidosis but its evolution and progression in different subregions of the GI tract are not well documented. These aspects including the chemical nature of GI amyloid were examined in the AHC mouse model of inflammation-associated reactive amyloidosis. C57BL/6 mice were infected intraperitoneally with 250 AHC. Paraffin sections from the stomach and the small and large intestines of AHC mice were stained at different time intervals with Congo red or immunocytochemically with monospecific RAA. The submucosal blood vessels at 1 week postinfection were found to be the first target of amyloid deposition. With time the amyloid deposits extended to the mucosa and the Peyer's patches and immunoreacted with RAA; ileum was the most severely affected region. Amyloid was extracted from the GI tract and purified by size exclusion chromatography using 5 M guanidine-formic acid, pH 3. The purified amyloid was identified by Western blotting using RAA and by partial N-terminal microsequencing up to 10 cycles. The GI amyloid showed homology with murine SAA2, although SAA2 mRNA is not expressed in murine GI tract. These results shows that (a) the GI amyloid is derived, similar to that of splenic/hepatic amyloid, from circulating SAA2 and (b) the GI tract submucosal blood vessels are the first target of AA deposition. The data also suggest that AA-mediated damage to the submucosal blood capillaries may lead to SAA leakage followed by cascading of AA deposition in other layers of the GI tract.
Li
W
W
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Chan
S L
SL
Chronopoulos
S
S
Bell
A
A
Ali-Khan
Z
Z
D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004443:Echinococcosis / Q000150:complications*; D004591:Electrophoresis, Polyacrylamide Gel; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000378:metabolism; D007150:Immunohistochemistry; D007420:Intestine, Large / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D000685:Serum Amyloid A Protein / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D013270:Stomach / Q000098:blood supply / Q000737:chemistry
D000685:Serum Amyloid A Protein