Fc Receptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy
Alexander Staudt, MD*,
Petra Eichler, PhD ,
Christiane Trimpert, Msc*,
Stephan B. Felix, MD*,* and
Andreas Greinacher, MD
* Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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Figure 1 Effects of Intact IgG/Antibody Fragments on Isolated, Field-Stimulated Rat Cardiomyocytes
Changes of calcium transients and systolic cell shortening during superfusion (% changes from baseline; mean ± SEM; n = 6 experiments for each patient’s/control sample) with: intact immunoglobulin (Ig)G from plasma of healthy blood donors (control IgG) and intact IgG from dilated cardiomyopathy (DCM) patients (DCM-IgG); F(ab')2 fragments of control IgG and of respective DCM-IgG; intact DCM-IgG after pre-incubation with the F(ab')2 fragments of control subjects and of respective DCM patients; intact DCM-IgG after pre-incubation of cardiomyocytes with human Fc fragments; and goat-anti-human-F(ab')-IgG after pre-incubation of cardiomyocytes with F(ab')2 fragments of control IgG and of respective DCM patients. +++p < 0.001 significantly different from control IgG; ***p < 0.001 significantly different from DCM-IgG.
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Figure 2 Summary of Functional Findings
Intact immunoglobulin (Ig)G of dilated cardiomyopathy (DCM) patients induced negative inotropic effects by binding via their Fab part to the antigenic epitope on cardiomyocytes and then via their Fc part to the Fc receptor IIa (FcR) (A). The F(ab')2 fragments of these antibodies inhibited the effect of intact DCM IgG (B), as did Fc fragments of normal IgG (C). Reconstitution of Fc parts by sequential incubation of cardiomyocytes with DCM F(ab')2 fragments and goat-anti-human F(ab') IgG induced a negative inotropic effect (D) comparable to findings for intact DCM IgG. A detailed description of Fc receptor cross linking is in the Discussion section. AG = antigen.
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