Mouse models of IgG- and IgM-mediated hemolysis.
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.
Schirmer
David A
DA
Department of Pathology, Columbia University, New York, NY 10023, USA.
Song
Shuh-Chyung
SC
Baliff
Jeffrey P
JP
Harbers
Stephanie O
SO
Clynes
Raphael A
RA
Krop-Watorek
Anna
A
Halverson
Gregory R
GR
Czerwinski
Marcin
M
Spitalnik
Steven L
SL
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
D000911:Antibodies, Monoclonal; D006021:Glycophorins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D017452:Receptors, IgG; D003165:Complement System Proteins