NON-IMMUNOLOGIC CONTACT URTICARIA AND MAST CELLS

这项提议的目标是审查参与 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，以及在 对防腐剂、调味品、香料和其他物质的反应 消费品中的添加剂。病理生理机制 NICU的死亡人数尚不清楚。在这个项目中，我们将使用组合 生化、形态、生理学和药理学 检测肥大细胞在调节细胞周期中作用的技术 对已关联到的多个代理的响应 新生儿重症监护室。使用已建立的连续纯肥大细胞系 从犬肥大细胞瘤我们将检查药物的能力 与NICU相关，导致预先形成的和新的- 产生了调解人。产品将用荧光法进行分析 以及放射免疫分析，高压液相色谱， 紫外吸收光谱和气相色谱/质量 光谱分析。来自分离细胞的生化数据将被 肥大细胞形态计量学和生化研究的比较 在活体内对狗皮肤的作用。我们将研究相互作用 NICU药物与物理、化学和炎症之间的关系 可能存在于体内的刺激，并将检查 皮肤中不同类型的肥大细胞和炎性细胞 调停这些反应。药理抑制剂和 拮抗剂将被用来试图调节这两种反应 分离的肥大细胞和皮肤中。离体纯桅杆的研究 体外培养的细胞提供了一种模型系统，用于检测 肥大细胞对NICU药物的反应；皮肤的活体研究 允许评估肥大细胞和 其他细胞类型。希望这些研究可以帮助提供 制定有效的治疗方案的方向 对于人类NICU，基于肥大细胞的预防 脱颗粒和/或预防肥大细胞诱导 发炎。

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.