The proposed work will study the biological role of specific IgE antibody in the rabbit at the physiologic, cellular and molecular level. These in vitro and in vivo studies are possible due to the development of an experimental model in our laboratory that allows for the preferential expression of only IgE antibody to various antigens with a complete suppression of IgG and IgM antibody production. Therefore, the biological role of specific IgE antibody can be studied unambiguously both in vivo and in vitro. Experiments will be performed to characterize the cardiovascular pulmonary alterations occurring in rabbits undergoing IgE-induced acute allergic reaction due to intravenous and inhalation antigen challenged. Following such characterization various interventions will be applied to the model to study the various pharmacologic and neurologic factors responsible for the development of cardiovascular pulmonary changes. Recently acquired information in our laboratory indicates that specific IgE antibody not only results in the degranulation of the blood basophil and tissue mast cell but leads to alterations in the blood platelet and neutrophil; furthermore, evidence has been obtained that various soluble, inflammatory plasma protein systems also are activated directly or indirectly by specific IgE antibody. Therefore, additional studies will be performed to determine whether IgE antibody can lead to the activation of the kallikrein, fibrinolytic and coagulation mechanisms and whether such activation is involved in the development of the physiologic manifestations of the IgE acute allergic reaction in vivo.