Implication of oxidative stress as a cause of autoimmune hemolytic anemia in NZB mice.
We have recently shown that deficiency of the superoxide dismutase 1 gene (SOD1) causes anemia and autoimmune responses against red blood cells (RBCs) and that transgenic expression of human SOD1 in erythroid cells rescues them. Because these phenotypes observed in SOD1-deficient mice are similar to autoimmune hemolytic anemia (AIHA), a causal connection between reactive oxygen species (ROS) and AIHA was examined using an AIHA-prone New Zealand Black (NZB) mouse. ROS levels in RBCs were high in young NZB mice, compared to control New Zealand White (NZW) mice, and increased during aging. Methemoglobin and lipid peroxidation products were elevated during aging, consistent with the elevated oxidative stress in RBCs of NZB mice. Severity of anemia and levels of intracellular ROS were positively correlated. Levels of antibodies against 4-hydroxynonenal and acrolein were also elevated in NZB mice. Transgenic expression of human SOD1 protein in RBCs of NZB mice suppressed ROS in RBCs and decreased the death rate. When RBCs from C57BL/6 mice were injected weekly into the same strain of mice, production of anti-RBC antibody was observed only in mice that had been injected with oxidized RBCs. Thus, oxidation-mediated autoantibody production may be a more general mechanism for AIHA and related autoimmune diseases.
Iuchi
Yoshihito
Y
Department of Biochemistry and Molecular Biology, Yamagata University, Japan.
Kibe
Noriko
N
Tsunoda
Satoshi
S
Suzuki
Saori
S
Mikami
Takeshi
T
Okada
Futoshi
F
Uchida
Koji
K
Fujii
Junichi
J
D000744:Anemia, Hemolytic, Autoimmune / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001323:Autoantibodies; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D001323:Autoantibodies; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1