Immune Netw.  2007 Sep;7(3):141-148. 10.4110/in.2007.7.3.141.

Anti-IgE mAb Suppresses Systemic Anaphylaxis through the Inhibitory IgG Receptor FcgammaRIIb in Mice: Interaction between Anti-IgE and FcgammaRIIb

• Kang NI
• Jin ZW
• Lee HK

• KMID: 1513200
• DOI: http://doi.org/10.4110/in.2007.7.3.141

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.

Keyword

anti-IgE mAb; anaphylaxis; FcgammaRIIb

MeSH Terms

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
Immunoglobulin E
Immunoglobulin Fc Fragments
Immunoglobulin G
Inositol
Papain
Penicillin V
Phosphoric Monoester Hydrolases
gamma-Globulins