Accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice.
Natural Abs have been implicated in initiating mesenteric ischemia/reperfusion (I/R)-induced tissue injury. Autoantibodies have affinity and self-Ag recognition patterns similar to natural Abs. We considered that autoimmunity-prone mice that express high titers of autoantibodies should have enhanced I/R-induced injury. Five-month-old B6.MRL/lpr mice displayed accelerated and enhanced intestinal I/R-induced damage compared with 2-mo-old B6.MRL/lpr and age-matched C57BL/6 mice. Similarly, older autoimmune mice had accelerated remote organ (lung) damage. Infusion of serum IgG derived from 5-mo-old but not 2-mo-old B6.MRL/lpr into I/R resistant Rag-1-/- mice rendered them susceptible to local and remote organ injury. Injection of monoclonal IgG anti-DNA and anti-histone Abs into Rag-1-/- mice effectively reconstituted tissue injury. These data show that like natural Abs, autoantibodies, such as anti-dsDNA and anti-histone Abs, can instigate I/R injury and suggest that they are involved in the development of tissue damage in patients with systemic lupus erythematosus.
Fleming
Sherry D
SD
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Monestier
Marc
M
Tsokos
George C
GC
D000818:Animals; D000974:Antibodies, Antinuclear / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003433:Crosses, Genetic; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000628:therapy
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D006657:Histones; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; C064658:RAG-1 protein