IGG1 AND IGE RECEPTOR MECHANISMS IN LUNG

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The guinea pig is an excellent model for studying pulmonary immediate hypersensitivity reactions. In this species, IgG1 is the major anaphylactic antibody, but IgE antibody can be produced under certain circumstances. For some time we have been studying the biologic activity of guinea pig IgE antibody as it relates to IgG1 reactivity and as a model of human IgE antibody activity in immediate hypersensitivity reactions. Therefore, the long range goal of our research has been and continues to be an understanding of the differences and relationships of IgG1 and IgE antibodies as they relate to pulmonary immediate hypersensitivity reactions in the guinea pig. The specific aims of our proposal are based upon three fundamentally important findings in our studies. Both IgG1 and IgE cause pulmonary smooth muscle contraction, but through separate receptors; differences in concentrations of mediators released when these receptors are activated; and evidence to suggest heterogenity of guinea pig lung mast cells. The questions we have formulated based upon these findings center around the issues of another mediator involved in the lung contractile responses, and whether different populations of mast cells (if they do exist) have IgG1 or IgE receptors on their surface and this is the basis for our tissue findings. Based upon techniques we have established in our laboratory, we will approach these questions in two ways. First, we will examine antibody sensitized pulmonary tissue utilizing the superfusion technique. In this procedure, both the contractile response and mediators released can be measured after antigen stimulation of sensitized tissue. In these experiments we will specifically be evaluating for other mediators (either released by mast cells or other pulmonary cells) involved in the contractile response. Second, we will isolate pulmonary mast cells from lung tissue, examine these cell suspensions for relationships and differences in mediator release mediated by IgG1 and IgE antibody, probe the isolated mast cell surface IgG1 and IgE antibody receptors, and examine these cells for functional and phenotypic heterogenity. Allergic disorders of the lung are important diseases occurring in many individuals. Our ability to examine the questions we have asked in both lung tissue and isolated lung cells gives us an important opportunity to investigate basic mechanisms of pulmonary immediate hypersensitivity reactions that could aid in our understanding of similar events in human lung.