Fibrillar amyloid-beta production, accumulation, and recycling in transgenic mice pancreatic acinar cells and macrophages

Autor: Henryk M. Wisniewski, Michal Tarnawski, Kuo-Chiang Wang, Cesare Mondadori, Joseph Nowakowski, Andy Giovanni, Mariusz Muzylak, Mikio Shoji, Eulalia Badmajew, Jerzy Wegiel
Rok vydání: 2000
Předmět:
Zdroj: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 7(2)
ISSN: 1350-6129
Popis: Amyloid-beta (A beta) production, accumulation, and recycling were examined by light and electron microscopy in the pancreas of transgenic mice (from 45 days to 22 months of age) that express the gene for the carboxy-terminal fragment of the human amyloid-beta protein precursor. Ultrastructural immunocytochemistry revealed four types of cells accumulating fibrillar A beta 1-40 in cytoplasmic vacuoles: acinar pancreatic cells, macrophages infiltrating stroma, epithelial cells of pancreatic ducts, and blood monocytes/macrophages in the lumen of pancreatic vessels. The ultrastructure of amyloid deposits suggests that each of these four types of cells produces fibrillar A beta. Three basic types of amyloid deposits were distinguished: primary vacuoles in different stages of amyloid aggregation and fibrillization, secondary vacuoles that are the product of fusion of primary vacuoles, and phagosome-like vacuoles with morphologically intact fibrillar amyloid and residues of ingested cells. Amyloid production in acinar pancreatic cells starts in mice younger than 45 days, progresses in 2- to 7-month-old mice, and plateaus in the second year of life. In macrophages, amyloid appears in 60-day-old mice, and the increase in the number of macrophages and the amount of amyloid in their cytoplasm correlates with age.
Databáze: OpenAIRE