CELLULAR BASIS OF HYPERSENSITIVITY DISEASES

这项正在进行的过敏性炎症研究的中心主题涉及 肥大细胞、嗜酸性粒细胞的发育受尼古丁调节， 5-脂氧合酶/白三烯（LT）C4合酶途径。的重要性 有证据支持半胱氨酰白三烯对支气管哮喘的作用 它们的过度生产和来自药物的临床益处 从而减弱其生产或作用。一个正在进行的项目， 城市内少数民族的哮喘发病率将转移其重点 从教育患者及其家人的临床益处中， 医生对哮喘的认识，以实现更多的参与， 患者人群处于危险之中。系统性肥大细胞增多症的发生 小鼠通过过继转移永生化V3肥大细胞， 组织定向分化和成熟的体内证明 单核细胞样祖细胞，允许分泌颗粒的研究 原位处理，并提出了一个模型，其中器官相关的纤维化 可以分析。人LTC 4基因cDNA的表达克隆 合酶，沿着LTC 4脱氢酶特异性抗体的开发， 允许定义细胞和亚细胞分布， 通过突变蛋白动力学研究进行免疫检测和功能。的 脐带血单核嗜酸性粒细胞的发育 来自正常人的分叶/超分叶功能性致敏嗜酸性粒细胞 嗜酸性粒细胞通过不同的培养系统提供了机会， 比较两种表型的生化特征， 低密度的、与疾病相关的嗜酸性粒细胞群。此外，本发明还提供了一种方法， 半胱氨酰组分的发育顺序 在嗜酸性粒细胞生成过程中， 通过分子、蛋白质和功能分析从脐带血中提取。最后， 本发明还提供了用于所述细胞的gp 49蛋白家族的cDNA和基因的克隆， 小鼠优先表达免疫球蛋白超家族 肥大细胞和巨噬细胞导致了gp 49家族的定义 以及观察到其成员介导细胞间相互作用， 活化的T细胞这一发现，以及分离出一个相关的cDNA， 粘附的人单核细胞/巨噬细胞，允许分析粘附 gp 49家族成员在两个物种中的功能，它们的细胞谱 表达，并通过细胞/细胞和固体寻找对应配体 分别用转染子和重组蛋白进行阶段测定。

The central theme of this ongoing study of allergic inflammation involves the cytokine-regulated development of mast cells, eosinophils, and the 5-lipoxygenase/leukotriene (LT)C4 synthase pathway. The importance of the cysteinyl leukotrienes to bronchial asthma is supported by the evidence of their over-production and by the clinical benefit derived from agents that attenuate their production or action. An ongoing project focused upon asthma morbidity among inner-city minorities will shift its emphasis from the clinical benefits of educating both patients and their physicians about asthma to achieving increased participation by the patient population at risk. The development of systemic mastocytosis in the mouse by adoptive transfer of immortalized V3 mast cells allows in vivo demonstration of the tissue-directed differentiation and maturation of monocytoid progenitors, permits studies of secretory granule processing in situ, and presents a model in which organ-related fibrosis can be analyzed. The expression cloning of the cDNA for human LTC4 synthase, along with the development of LTC4 synthase-specific antibody, allows definition of cellular and subcellular distribution by immunodetection and function by kinetic studies of mutated protein. The development of mononuclear eosinophils from cord blood and of segmented/hypersegmented functionally-primed eosinophils from normal eosinophils by different culture systems provides the opportunity to compare the biochemical characteristics of two phenotypes observed among the hypodense, disease-associated eosinophil populations. In addition, the developmental sequence for the components of the cysteinyl leukotriene-generating pathway can be defined during eosinophilopoiesis from cord blood by molecular, protein, and functional analyses. Finally, the cloning of the cDNAs and genes for the gp49 family of proteins of the immunoglobulin superfamily that are preferentially expressed by mouse mast cells and macrophages has led to the definition of the gp49 family and the observation that its members mediate cell-cell interactions with activated T cells. This finding, and the isolation of a related cDNA from adherent human monocyte/ macrophages, allows an analysis of the adhesion function of gp49 family members in two species, their cell profile of expression, and the search for the counter ligands by cell/cell and solid phase assays with transfectants and recombinant proteins, respectively.