Korean Journal of Nephrology 1994;13(1):13-34.

신장의 AA형 아밀로이드 형성기전에 관한 초미형태학적 연구

박관규 , 김영호 , 손태중

Abstract

Renal amyloidosis was induced in a group of ICR mice by daily subcutaneous injections of casein- endotoxin solution to clarify the pathogenentic me- chanism of renal glomerular amyloidosis. The mice were sacrificed at 1, 2, 3, 4, 5, 6 and 7 weeks after the last injection of casein-endotoxin. The kidneys were processed for light and electron microscopy. Amyloid deposits were investigated on light microscopy, immunohisto- chemistry by the PAP method, electron microscopy and ultrathin section using the protein-A gold method. Light microscopically, the distribution of amyloid in the glomerulus was not diffuse but focal and nodular leaving some portions of the capillary walls intact even in the heaviest lesion. Electron microscopically, amyloid fibrils were demonstrated predominantly in the mesangial matrix and could be seen penetrating the basement membrane of the mesangial region into the subepithelial and subendothelial space of adjacent glomerular capil- laries. The basement membrane is not primarily involved in amyloidosis, but is secondarily infiltrated by heavy amyloid deposition. These amyloid fibrils were arranged in random array as thin, rigid and nonbranch- ing fibrils. With increasing amounts of amyloid, the mesangium became widened and the mesangial cell cytoplasm diminished in amount. The glomerular cells - whether they are mesangial, endothelial or epithelial cells - contain an abundance of free rebosomes, polysomal aggregates, endoplasmic reticulum and Golgi apparatuses. The intimate structural relationships of the tufts of amyloid fibrils to mesangial cells, as well as to the endothelial and epithelial cells were observed. Membrane surrounded amyloid fibrils were found within the cytoplasm of the mesangial and epithelial cells. These are most likely the result of cross sections or oblique sections of the invagination of the amyloid to the cyoplasm of the cells. The cytoplasmic membrane or the membrane surrounding the intracellular amyloid fibrils appears inc.stinct at the particular site of appar- ent amyloid formation. Many vesicles and vacuoles are also found near the cytoplasmic membrane of the cells. Using the postembedding protein-A gold technique, monoclonal antibodies directed against amyloid-A protein (AA) were examined by immunoelectron micros- copy to identify the fibrils. Many gold particles labelled fibrillar structure were seen in the extracellular space. It is concluded by our morphologic findings that amyloid fibrils in the glomerulus are formed from amyloid precursors brought via the blood stream and may be formed in the extracellular space under the lysosomal enzyme released from epithelial, mesangial and perhaps endothelial cells.