Immunoglobulin E–dependent active fatal anaphylaxis in mast cell–deficient mice

IH Choi, YM Shin, JS Park, MS Lee, EH Han… - The Journal of …, 1998 - rupress.org
IH Choi, YM Shin, JS Park, MS Lee, EH Han, OH Chai, SY Im, TY Ha, HK Lee
The Journal of experimental medicine, 1998rupress.org
Mast cells have long been believed to be the central effector cells in the development of
immunoglobulin (Ig) E-dependent anaphylaxis. In this study, we investigated the role of mast
cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell–deficient
WBB6F1-W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock
signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V)
occurred in both+/+ and W/Wv mice. Administration of monoclonal anti–IL-4 antibody …
Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell–deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti–IL-4 antibody completely prevented the fatal reactions, and the effect of anti–IL-4 was associated with its suppressive activity on Pen V–specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.
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