Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic mice.
We previously demonstrated that increased Fas expression in T cells of aged CD2-fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the average life span of Fas-Tg mice is comparable with that of nontransgenic (non-Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy. The full-length amino acid coding sequence of serum amyloid A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible BALB/c mice. Although there was no significant difference in steady-state serum amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice with staphylococcal enterotoxin B resulted in significantly higher serum levels of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of weight loss on day 7 in aged Fas-Tg mice compared with young mice. These parameters, at the indicated time points, were equivalent between young and aged non-Tg mice. Taken together, our data suggest that prevention of T cell senescence in Fas-Tg mice may be a factor in induction of an excessive acute-phase response triggered by T cell activation. The Fas-Tg mice are a novel model for understanding the immunologic mechanisms leading to secondary amyloidosis.
Hsu
H C
HC
Department of Medicine, University of Alabama at Birmingham, and the Birmingham Veterans Administration Medical Center, 35294, USA.
Zhou
T
T
Yang
P A
PA
Herrera
G A
GA
Mountz
J D
JD
D000210:Acute-Phase Reaction / Q000276:immunology*; D000375:Aging / Q000276:immunology*; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D018801:CD2 Antigens / Q000032:analysis*; D016922:Cellular Senescence / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology*; D007678:Kidney Glomerulus / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D000685:Serum Amyloid A Protein / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000032:analysis*
D018801:CD2 Antigens; D000685:Serum Amyloid A Protein; D019014:fas Receptor