Ubiquitin profile in inflammatory leukocytes and binding of ubiquitin to murine AA amyloid: immunocytochemical and immunogold electron microscopic studies.
Lysosomes in activated murine monocytoid cells have been implicated in AA amyloid formation. The pathophysiology of this process is not well understood. Previous studies into the nature of the relationship between ubiquitin (UB), possessing intrinsic amyloid enhancing factor (AEF) activity; serum amyloid A (SAA), the precursor protein of AA amyloid; and activated monocytoid cells have indicated a temporal and spatial relationship between these proteins and tissue AA amyloid deposits. To extend these findings, we have examined murine peritoneal leukocytes and splenic tissues during the early amyloid deposition phase by immunocytochemical and immunogold electron microscopic methods using monospecific anti-ubiquitin and anti-mouse AA amyloid antibodies. We show here enrichment of endosome-lysosome-like (EL) vesicles in the activated monocytoid cells with UB and SAA, and the presence of UB-bound AA amyloid fibrils in the EL vesicles, perikarya, and interstitial spaces. The importance of these findings is emphasized by the fact that activated monocytoid cells, containing UB in the EL vesicles, sequester and eventually localize SAA in their EL vesicles, and that UB binds to the EL-contained AA amyloid fibrils. These findings may also have functional consequences for studies on the role of EL and UB in amyloidogenesis.
Alizadeh-Khiavi
K
K
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Li
W
W
Chronopoulos
S
S
Ali-Khan
Z
Z
D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007962:Leukocytes / Q000737:chemistry*; D008247:Lysosomes / Q000737:chemistry; D008264:Macrophages / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009504:Neutrophils / Q000737:chemistry; D010537:Peritoneum / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000032:analysis*; D013154:Spleen / Q000737:chemistry*; D014452:Ubiquitins / Q000032:analysis*
D000685:Serum Amyloid A Protein; D014452:Ubiquitins