Regulation of Human Mast Cell Function

描述（由申请人提供）：赵博士的长期目标是发展成为一名独立的医生科学家，具有识别研究机会并构建合理性和可实现的策略来解决这些机会的技能和成熟度。 先进的课程和指导相结合，应该使这成为可能。劳伦斯博士B。施瓦茨将担任导师。 赵医生最近加入了VCU，从2003年7月开始担任儿科助理教授。 研究空间已提供儿科沿着与工资支持和保护的时间。 人肥大细胞是获得性免疫的效应细胞，也可能是先天性免疫的效应细胞。 它们在血管周围和皮肤、胃肠道和肺组织中丰富。 获得在培养物中增殖并保留原始肥大细胞的功能表型的高纯度人皮肤来源的肥大细胞的能力为研究此类细胞提供了关键工具。 目前的建议将检查这些肥大细胞和细胞因子之间的关系，以及肥大细胞在慢性荨麻疹发病机制中的作用。 目的1研究人皮肤源性肥大细胞经FcepsilonRI激活后产生的细胞因子和脂质介质。 由于初步结果表明，许多细胞因子在其释放期间或释放后不久被降解，推测是通过共释放的肥大细胞蛋白酶，因此将开发条件以防止其降解，从而了解其产生的全部程度。 目的2将检测细胞因子调节通过IgE和IgG受体激活的肥大细胞产生细胞因子和前列腺素和白三烯的能力。 目的3将表征慢性荨麻疹患者血清标记人皮肤源性肥大细胞表面并激活或引发人皮肤源性肥大细胞的能力。 了解人类肥大细胞的这些功能属性将提供深入了解过敏性疾病的发病机制，并可能揭示新的治疗靶点。

DESCRIPTION (provided by applicant): The long-term goal is for Dr. Zhao to develop as an independent physician scientist with the skill and maturity to identify research opportunities and to construct rationale and achievable strategies to address these opportunities. The combination of advanced coursework and mentoring should make this possible. Dr. Lawrence B. Schwartz will serve as mentor. Dr. Zhao recently joined the VCU as an Assistant Professor of Pediatrics beginning July, 2003. Research space has been provided within the Department of Pediatrics along with salary support and protected time. Human mast cells are effector cells of acquired and probably innate immunity. They are abundant around blood vessels and in cutaneous, gastrointestinal and pulmonary tissues. The ability to obtain human skin-derived mast cells of high purity that proliferate in culture and retain the functional phenotype of the original mast cells provides a critical tool for research on such ceils. The current proposal will examine relationships between these mast cells and cytokines, and the role of such mast cells in the pathogenesis of chronic urticaria. Aim 1 will characterize the cytokines and lipid mediators produced by human skin-derived mast cells activated through FcepsilonRI. Because preliminary results indicate many of the cytokines are degraded during or shortly after their release, presumably by co-released mast cell proteases, conditions will be developed to prevent their degradation and thereby appreciate the full extent of their production. Aim 2 will examine the ability of cytokines to regulate cytokine production and prostaglandin and leukotriene generation by mast cells activated through IgE and IgG receptors. Aim 3 will characterize the ability of sera from patients with chronic urticaria to label the surface of and to activate or prime human skin-derived mast cells. Understanding these functional attributes of human mast cells will provide insights into the pathogenesis of allergic disease and may reveal new therapeutic targets.