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KMID : 0923620070070030141
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Immune Network
2007 Volume.7 No. 3 p.141 ~ p.148
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Anti-IgE mAb Suppresses Systemic Anaphylaxis through the Inhibitory IgG Receptor Fc?RIIb in Mice - Interaction between Anti-IgE and Fc?RIIb -
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Kang Nam-In
Lee Hern-Ku
Jin Zhe-Wu
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Abstract
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Background: Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis.
Methods: Active systemic anaphylaxis was induced by either penicillin V (Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse Fc?RIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry.
Results: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in Fc?RIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine Fc?RIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of Fc?RIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN).
Conclusion: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, Fc?RIIb, rather than targeting IgE.
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KEYWORD
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anti-IgE mAb, anaphylaxis, Fc?RIIb
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