This proposal is designed to elucidate the in vivo activity of IgE antibody in a rabbit model and to elucidate the specific mediators, cells and physiologic mechanisms by which this antibody leads to the alterations in respiratory and circulatory function which are characteristic of acute allergic reactions. Two types of responses will be studied and compared: systemic anaphylaxis as a result of intravenous antigen challenge and asthma-like bronchoconstriction induced by aerosolized antigen. Roles for histamine, AGEPC, basophils, and platelets in the aerosol antigen response will be compared with those already established for anaphylaxis. We will determine if prostaglandins and/or leukotrienes are important mediators of any of the individual alterations in either response by a) comparing the circulatory and respiratory alterations induced by these agents to those induced by antigen and/or b) demonstrating their in vivo release following antigen challenge and c) determining the effects of agents which block their synthesis (ibuprofin, imidazole, ETYA) or activity (FPL55712) on the antigen-induced response. In vitro correlative studies will include use of isolated pulmonary arteries, bronchi and lung parenchyma to establish mechanisms of alterations in right ventricular pressure and lung mechanics. Effects of in vivo neutrophil depletion will be examined as will in vitro involvement of neutrophils (as secondarily stimulated cells) in mediator release. Purified IgE will be given to normal rabbits to examine our contention that IgE alone is necessary and sufficient to confer sensitivity to anaphylaxis and/or response to aerosolized antigen. We will establish threshold levels for IgE and determine the effects of various levels of specifi IgG. Finally, physiologic and histologic evidence of the occurrence of an IgE-induced late phase reaction (LPR) will be sought. If LPRs occur, their dependence on IgE level prostaglandin-synthesis, and circulating neutrophils will be determined.
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