Cytochemical study of the involvement of cell organelles in formation and accumulation of fibrillar amyloid in the pancreas of NORβ transgenic mice

• Dobrogowska, D. H. ^[1] ; Vorbrodt, A. W. ^[1] ; Wegiel, J. ^[1] ; Wang, K.-C. ^[1] ; Shoji, M. ^[2] ; Mondadori, C. ^[3] ; Polatis, G. ^[3] ; Giovanni, A. ^[3] ; Wisniewski, H. M. ^[1]
  1. [1] New York State Energy Research and Development Authority

     New York State Energy Research and Development Authority

     City of Albany, Estados Unidos

     
  2. [2] Gunma University

     Gunma University

     Japón

     
  3. [3] Aventis Pharmaceuticals, Bridgewater, NJ, USA

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 4, 2001, págs. 1047-1056
• Idioma: inglés
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  • Phosphatase ultrastruc tural cytochemistr y was used to evaluate the participatio n of cytoplas mic o rganelles in the acc umulation of fibrillar amyloid /3 (A13) in exocrine acinar cells and in mac rophages of the pancreas of transgenic mice overexpressing a carboxy-te rminal fragment o f A/3 prote in precur sor (A/3PP) . Nuc leoside diphosphatase (NDPase) and g lucose-6-phospha tase (G 6 Pase) w e re use d as cytoche mic al marke rs of the endoplasmic reticulum (ER), thiamine pyrophosphatase (TPPase) as a marke r of the Go lg i apparatus (GA), and acid phosphatase (AcPase) as a marker of Iysoso mes. Monocl onal antibody 4G8 raised against the 17-24 aa sequence of human A/3 protein was use d for immunogold localizatio n of fibrillar A/3. The res ults of this study indica te that the formation of A13 in acinar cells occurs directly in the vacuolar areas of the ro ug h ER ( RER) without evident participatio n o f the e le ments of the GA, whe reas a n intima te structura l relation with primary Iysosomes s ugges ts their role in modification or digestio n of the deposited amyloid. In mac rophagcs, fibrillar amyloid was pr esent in numero us cytoplas mic vac uo les located frequently in c lose proximity to flatte ned sa ccules of the ER. This structural pattern revealed similarit y to that o bserved previo usly in mic roglia l cells producing fibrillar PrP amyloid in scrapie-infected mice and A/3 in br ains of human elderly patients and in Alzheimer's type br ain pathology.