NON-IMMUNOLOGIC CONTACT URTICARIA & MAST CELLS

这项建议的目的是审查参与 非免疫性接触性荨麻疹（NICU）中的肥大细胞。 NICU 工业和职业暴露的结果， 对防腐剂、调味剂、香料和其他 消费品中的添加剂。 病理生理机制 NICU的情况不详。 在这个项目中，我们将使用一个组合 生物化学形态学生理学和药理学 技术来检查肥大细胞在调节 对一些与之有关联的代理人的回应 新生儿重症监护室 使用已建立的连续纯肥大细胞系， 从犬肥大细胞瘤中，我们将检查药物的能力， 与新生儿重症监护室相关，导致释放预先形成和新- 产生的调解人。 产品将通过荧光分析 放射免疫分析，高压液相色谱， 紫外吸收光谱和气相色谱/质谱 光谱法 分离细胞的生化数据将 与肥大细胞的形态计量学和生物化学研究相比， 在犬皮肤中的作用。 我们将研究 NICU药物与物理、化学和炎症之间的关系 刺激可能存在于体内，并将检查的作用， 不同类型的肥大细胞和炎症细胞在皮肤中， 调解这些反应。 药理学抑制剂和 拮抗剂将被用来试图调节这些反应，在这两个 分离的肥大细胞和皮肤。 分离纯肥大细胞研究 体外细胞提供了一个模型系统， 肥大细胞对NICU药物的反应;皮肤中的体内研究 允许评估肥大细胞之间的相互作用， 其他细胞类型。 希望这些研究能帮助我们 制定有效治疗方案的方向 用于人类NICU，基于预防肥大细胞 脱粒和/或防止肥大细胞诱导的 炎症

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.