Rat Monoclonal Anti-Murine IgE Antibody Removes IgE Molecules Already Bound to Mast Cells or Basophilic Leukemia Cells, Resulting in the Inhibition of Systemic Anaphylaxis and Passive Cutaneous Anaphylaxis

Abstract

IgE plays a central role in allergic reactions. Some anti-IgE antibodies (HMK-12, 6HD5) inhibit the binding of IgE to the FcΕRI of mast cells/basophilic leukemia cells (PT-18, RBL/2H3), but less inhibition is seen with the anti-allotypic JKS-6 and the anti-idiotypic Eb-1. Anti-IgE HMK-12 can detach bound IgE molecules from the FcΕRI. When mast cells or basophils were incubated with monoclonal anti-DNP-IgE SPE-7, washed and treated with anti-IgE HMK-12, anti-IgE/IgE complexes were found in the supernatant. Similar results were obtained with the Fab fragment of HMK-12. Mice injected with anti-DNP-IgE SPE-7 and later with DNP-BSA had the typical systemic anaphylactic shock. However, if they were injected with the anti-IgE antibody (HMK-12) before the challenge, they did not get an anaphylactic shock. In the sera of mice injected with monoclonal IgE SPE-7 and anti-IgE antibody (HMK-12), IgE/anti-IgE complexes were detected. No passive cutaneous anaphylaxis occurred if the rats were injected with anti-IgE antibodies before the challenge. In summary, anti-IgE antibodies can remove IgE antibodies from the FcΕRI; anti-IgE/IgE complexes can be detected in vitro and in vivo, and anti-IgE antibodies can inhibit IgE-mediated systemic or local anaphylactic reactions.

The Fab fragment of anti-IgE Cε2 domain prevents allergic reactions through interacting with IgE-FcεRIα complex on rat mast cells

“…However, deletion of the Cε2 domain from the IgE H chain constant region increased the rate of dissociation of IgE from the receptor, which suggests that the IgE Cε2 domain plays a pivotal role in stabilizing the interaction of IgE with FcεRIα 36 . These findings support our previous observations that indicate that some anti-IgE antibodies, including 6HD5, can remove an IgE molecule already bound to FcεRIα on the surface of mast cells or basophilic leukemia cells and inhibit IgE-mediated systemic or local anaphylactic reactions 33 , 37 .…”

“…These antibodies are thought to recognize the binding sites of IgE for FcεRIα. We have previously shown that the anti-IgE antibody HMK-12 also inhibits the binding of IgE to the IgE-FcεRIα complex 33 . By contrast, Fab-6HD5 appears to suppress the release of chemical mediators after IgE antigen-mediated crosslinking of surface FcεRIα, which indicates that this antibody is not a competitive inhibitor of the IgE-FcεRIα interaction.…”

“…SPE-7 (anti-DNP murine IgE antibody) and 141a (anti-TNP murine IgE antibody) were purchased from Sigma-Aldrich Co. LLC (USA) and Pharmingen (USA), respectively. The rat monoclonal antibodies 6HD5 and HMK-12 (specific for murine IgE) have been described previously 33 , 37 . The rat IgG anti-murine κ antibody and phycoerythrin (PE)-labeled goat anti-rat IgG were purchased from BioLegend (CA, USA) and Jackson ImmunoResearch (PA, USA) respectively.…”

Factors Associated with Echinococcosis-Induced Perioperative Anaphylactic Shock

“…IgG is involved in anaphylactic shock or even death induced by antigens of parasites alongside IgE [ 14 , 21 ]. IgG accounts for about 75–80% of all immunoglobulins in the serum, and consists of 4 subtypes, IgG1, IgG2, IgG3, and IgG4 [ 22 ].…”

Allosteric inhibition of IgE–FcεRI interactions by simultaneous targeting of different epitopes on IgE F(ab’)2

“…Monoclonal antibodies SPE-7 IgE (anti-DNP murine IgE antibody) and SPE-7 IgE F(ab')2 were purchased from Sigma-Aldrich Co. LLC (USA) and Immuno-Biological Laboratories Co., Ltd. (Gunma, JAPAN), respectively. The rat monoclonal antibody HMK-12 (speci c for murine IgE) was used as described previously 30,37 . Rat IgG anti-murine κ antibodies and HRP-labelled goat anti-rat IgG were purchased from BioLegend (CA, USA) and Jackson ImmunoResearch (PA, USA), respectively.…”