Du T, Ali-Khan Z
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
J Exp Pathol (Oxford). 1990 Jun;71(3):313-35.
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.
使用感染了10个、50个或250个肺泡包虫囊肿（AHC）的C57BL/6小鼠来研究继发性淀粉样变性的发病机制。对脾脏切片进行免疫和酶组织化学分析，以研究AHC抗原、血清淀粉样蛋白A（SAA）和淀粉样蛋白（AA）沉积之间的时间关系，以及在淀粉样变性发生之前和期间脾边缘区（MZ）和红髓网状内皮（RE）细胞中溶酶体酸性磷酸酶（AP）和非特异性酯酶（NSE）浓度的定性和定量变化。AA诱导期从50个囊肿组的5周缩短至250个囊肿组的6或7天；10个囊肿组的小鼠脾脏AA仍为阴性。在AA沉积之前，脾脏RE细胞增生、AHC抗原和SAA沉积以及脾细胞中AP和NSE活性达到峰值。MZ中的AA沉积与RE细胞AP和NSE活性降低以及MZ中的退行性变化同时发生。在静脉注射对RE细胞具有细胞毒性的二氧化硅后，250个囊肿组的AA诱导期从7天进一步缩短至4天。我们认为，由于溶酶体酶逐渐减少以及脾MZ单核样细胞发生退行性变化，导致组织部位SAA清除缺陷，从而触发细胞外基质中的淀粉样变性。
