Ubiquitin: its potential significance in murine AA amyloidogenesis.
Amyloid enhancing factor (AEF), which has recently been shown to have identity with ubiquitin (Ub), is believed to play a causative role in experimentally induced AA amyloidosis in mice. We have examined the profile of Ub in activated leukocytes and splenic reticulo-endothelial (RE) cells and its relationship with serum amyloid A protein (SAA) and AA amyloid deposits in an alveolar hydatid cyst (AHC)-infected mouse model of AA amyloidosis. Two monospecific antibodies, anti-ubiquitin (RABU) and anti-mouse AA amyloid, were used as immunological probes to localize Ub, SAA, and AA amyloid. In response to AHC infection, the dull and diffuse Ub immunoreactivity in normal mouse leukocytes and RE cells promptly changed to a discrete granular pattern suggesting an increase in the intracellular concentration of Ub and the formation of Ub-protein conjugates. This corresponded to an elevation in SAA levels, SAA uptake by RABU-positive phagocytic cells, co-localization of Ub-SAA immunoreactive splenocytes in the perifollicular areas, and deposition of Ub-bound AA amyloid in the splenic and hepatic tissues. These results suggest that Ub-loaded monocytoid cells may play an important role in the physiological processing of the sequestered SAA into AA amyloid. Aspects of AA amyloidogenesis are discussed in relation to other experimental models in which stress-induced Ub-protein conjugate formation and its transport to lysosomal vesicles have been studied.
Chronopoulos
S
S
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Lembo
P
P
Alizadeh-Khiavi
K
K
Ali-Khan
Z
Z
D000682:Amyloid / Q000032:analysis / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology*; D000818:Animals; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000378:metabolism*; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D014452:Ubiquitins / Q000032:analysis / Q000378:metabolism*
D000682:Amyloid; D006023:Glycoproteins; D000685:Serum Amyloid A Protein; D014452:Ubiquitins; C046748:amyloid enhancing factor