title: Mouse models of IgG- and IgM-mediated hemolysis.
abstract: Well-characterized mouse models of allo-immune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine "blood group system," mRBCs from hGPA-Tg mice are "antigen positive" and mRBCs from non-Tg mice are "antigen negative." Passive immunization of non-Tg mice with the IgG1 10F7 and IgG3 NaM10-2H12 anti-hGPA mAbs each induced rapid clearance of incompatible transfused hGPA-Tg-mRBCs in a dose-response manner. Using various knockout mice as transfusion recipients, both the complement system and activating Fcgamma receptors were found to be important in the clearance of incompatible mRBCs by each of these IgG mAbs. In addition, the IgM E4 anti-hGPA mAb induced complement-dependent intravascular hemolysis of transfused incompatible hGPA-Tg-mRBCs accompanied by gross hemoglobinuria. These initial studies validate the relevance of these new mouse models for addressing important questions in the field of transfusion medicine.
authors.affiliation: Department of Pathology, Columbia University, New York, NY 10023, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schirmer
authors.forename: Shuh-Chyung
authors.initials: SC
authors.lastname: Song
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Baliff
authors.forename: Stephanie O
authors.initials: SO
authors.lastname: Harbers
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Clynes
authors.forename: Anna
authors.initials: A
authors.lastname: Krop-Watorek
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Halverson
authors.forename: Marcin
authors.initials: M
authors.lastname: Czerwinski
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D003165:Complement System Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006021:Glycophorins / Q000235:genetics; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000097:blood; D065227:Transfusion Reaction
chemical_list: D000911:Antibodies, Monoclonal; D006021:Glycophorins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D017452:Receptors, IgG; D003165:Complement System Proteins