Inhibition of primates performed xenoantibody binding to pig aortic endothelial cells and its potential application to xenotransplantation.
IgM xenoantibodies are believed to play the most important role in the hyperacute rejection of distantly related species. The purpose of this study was to determine whether DL-Penicillamine could inactivate binding and cytotoxicity of adult baboon performed xenoantibodies to pig endothelial cells. Different concentrations of DL-Penicillamine were used to treat pooled baboon serum over various lengths of time. In order to determine the reactivity of baboon natural xenoantibodies to pig endothelial cells complement-mediated cytotoxicity assay was used. ELISA assay was used to assess IgM and IgG binding to pig endothelial cells. Subsequently DL-Penicillamine was dialyzed to determine its potential clinical application. Results indicate that baboon performed xenoantibodies class IgM and IgG bind to pig endothelial cells, but only IgM xenoantibody is cytotoxic DL-Penicillamine treatment can significantly reduce cytotoxicity and eliminate binding of IgM xenoantibodies to pig endothelial cells despite continued binding of IgG xenoantibodies to pig endothelial cells. In addition, DL-Penicillamine can be dialyzed, suggesting that it may be applicable in xenotransplantation and its toxicity can be significantly reduced by routine hemodialysis.
Kwiatkowski
P
P
Department of General and Transplantation Surgery, Warsaw Medical School, Poland.
Mazurek
A P
AP
Rowiński
W
W
Fiedor
P
P
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D010215:Papio; D010396:Penicillamine / Q000494:pharmacology; D013552:Swine; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010396:Penicillamine