The objective of this proposal is to examine the involvement of mast cells in non-immunologic contact urticaria (NICU). NICU results from industrial and occupational exposures, and in response to preservatives, flavorings, fragrances and other additives in consumer products. The pathophysiologic mechanism of NICU is not known. In this project we will use a combination of biochemical, morphologic, physiologic and pharmacologic techniques to examine the role of mast cells in modulating the response to a number of agents which have been associated with NICU. Using established continuous pure mast cell lines derived from canine mastocytomas we will examine the ability of agents associated with NICU to cause release of preformed and newly- generated mediators. Products will be analyzed by fluorometric and radioimmunoassays, high-pressure liquid chromatography, ultraviolet absorption spectra, and gas chromatography/mass spectrometry. Biochemical data from isolated cells will be compared with morphometric and biochemical studies of mast cell function in dog skin in vivo. We will examine the interaction between NICU agents and physical, chemical and inflammatory stimuli which may be present in vivo, and will examine the role of different types of mast cells and inflammatory cells in the skin in mediating these responses. Pharmacologic inhibitors and antagonists will be used to try to modulate these responses in both isolated mast cells and in skin. Studies with isolated pure mast cells in vitro provide a model system for examining the role of mast cells in the responses to NICU agents; in vivo studies in skin permit an assessment of the interaction between mast cells and other cell types. Hopefully, these studies may help to provide direction for the development of an effective treatment program for NICU in humans, based on prevention of mast cell degranulation and/or prevention of mast cell-induced inflammation.
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