Immunoglobulin E–dependent Active Fatal Anaphylaxis in Mast Cell–deficient Mice

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/W(v) (W/W(v)) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/W(v) mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/W(v) 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/W(v) mice, high levels of PAF in the circulation after challenge in both +/+ and W/W(v) 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.