This project employs convergent electrophysiological, biochemical and immunologic studies in the effort to elucidate mechanisms and consequences of immune hypersensitivity states at the cellular level. The interaction between mast cells and vagal afferents continues to be viewed in a pivotal role, since the involvement of mast cells in producing the inflammatory mediators of immediate hypersensitivity is well established. This in vitro work centers on the complex interactions between mast cells and vagal afferents which are implicated in hypersensitivity diseases such as asthma. Using intracellular recording techniques, cell bodies of vagal afferents housed in the nodose and jugular ganglia of actively sensitized animals will be characterized electrophysiologically before, during and after antigenic stimulation of local mast cells. Membrane currents, voltages and intracellular second messengers will be analyzed and manipulated in order to clarify the ionic basis of excitability changes wrought by inflammatory autacoids. Single-cell fluorescence techniques will be utilized in this phase of the study. Correlation of specific electrophysiological properties and chemoreception of somatic membranes with particular sensory modalities subserved by individual neurons will be pursued. A strain of mast cell-deficient mice will be used in order to discern whether cells other than mast cells contribute to antigen-induced excitability changes. These multidisciplinary studies will add to our understanding of the physiology of vagal afferents. We hope that this study of the signal molecules and mechanisms underlying mast cell-nerve interaction will also shed new light on the pathobiology of myriad hypersensitivity and inflammatory diseases.
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