Pathogenesis of secondary amyloidosis in an alveolar hydatid cyst-mouse model: histopathology and immuno/enzyme-histochemical analysis of splenic marginal zone cells during amyloidogenesis.
C57BL/6 mice infected with 10, 50 or 250 alveolar hydatid cysts (AHC) were used to study the pathogenesis of secondary amyloidosis. Immuno and enzyme-histochemical analyses on spleen sections were performed to investigate the temporal relationship between AHC antigen, serum amyloid A protein (SAA) and amyloid (AA) deposition and concomitant qualitative and quantitative changes in the concentration of lysosomal acid phosphatase (AP) and nonspecific esterase (NSE) in splenic marginal zone (MZ) and red pulp reticuloendothelial (RE) cells prior to and during amyloidogenesis. AA-induction period was reduced from 5 weeks in the 50 cyst group to 6 or 7 days in the 250-cyst group; the 10-cyst group mice remained negative for splenic AA. Splenic RE cell hyperplasia, deposition of AHC antigen and SAA and peak AP and NSE activities occurred in splenocytes prior to AA deposition. AA-deposition in the MZs coincided with reduced RE cell AP and NSE activities and degenerative changes in the MZs. AA-induction period in the 250-cyst group was further reduced from 7 days to 4 days after intravenous injection of silica which is cytotoxic to RE cells. We suggest that defective clearance of SAA from tissue sites as a result of progressive reduction in lysosomal enzymes coupled with degenerative changes in splenic MZ monocytoid cells trigger amyloidogenesis in the extracellular matrix.
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Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Ali-Khan
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D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology*; D000818:Animals; D000947:Antigens, Helminth / Q000032:analysis; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D004195:Disease Models, Animal; D004445:Echinococcosis, Pulmonary / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D004446:Echinococcus / Q000276:immunology; D007124:Immunoenzyme Techniques; D007958:Leukocyte Count; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012822:Silicon Dioxide / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism*
D000682:Amyloid; D000947:Antigens, Helminth; D012822:Silicon Dioxide; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase