Anti-IgE mAb Suppresses Systemic Anaphylaxis through the Inhibitory IgG Receptor FcgammaRIIb in Mice: Interaction between Anti-IgE and FcgammaRIIb.
- Author:
Nam In KANG
1
;
Zhe Wu JIN
;
Hern Ku LEE
Author Information
- Publication Type:Original Article
- Keywords: anti-IgE mAb; anaphylaxis; FcgammaRIIb
- MeSH: Anaphylaxis*; Animals; Asthma; Blotting, Western; Cell Line; CHO Cells; Cricetinae; Digestion; Down-Regulation; Flow Cytometry; gamma-Globulins; Immunoglobulin E; Immunoglobulin Fc Fragments; Immunoglobulin G*; Immunohistochemistry; Inositol; Lung; Mice*; Ovum; Papain; Penicillin V; Phosphoric Monoester Hydrolases
- From:Immune Network 2007;7(3):141-148
- CountryRepublic of Korea
- Language:English
- Abstract: 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 FcgammaRIIb 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 FcgammaRIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine FcgammaRIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of FcgammaRIIb-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, FcgammaRIIb, rather than targeting IgE.
