CELLULAR BASIS OF HYPERSENSITIVITY DISEASES

这项正在进行的过敏性炎症研究的中心主题包括 细胞因子调控的肥大细胞、嗜酸性粒细胞和 5-脂氧合酶/白三烯(LT)C4合成酶途径。重要的一点是 半胱氨酰白三烯治疗哮喘的证据支持 它们的过度生产和从药物中获得的临床益处 这削弱了他们的生产或行动。一个正在进行的项目，专注于 市中心少数民族的哮喘发病率将转移重点 从教育患者和患者的临床益处来看 医生对哮喘的看法，以实现更多的参与 患者群体处于危险之中。全身性肥大细胞增多症的进展 通过过继转移永生化的V3肥大细胞，小鼠允许 组织定向分化成熟的活体演示 单核细胞造血祖细胞，允许研究分泌颗粒 原位处理，并提出了一种器官相关性纤维化的模型 可以分析。人LTC4基因的表达克隆 合成酶，随着LTC4合成酶特异性抗体的研制， 允许通过以下方式定义蜂窝和亚蜂窝分布 通过突变蛋白的动力学研究进行免疫检测和功能。这个 脐血和成人单核嗜酸性粒细胞的培养 节段性/超节段性功能启动的正常嗜酸性粒细胞 嗜酸性粒细胞通过不同的培养系统提供了机会 比较观察到的两种表型的生化特性 低密度的、与疾病相关的嗜酸性粒细胞。此外, 半胱氨酸基组成成分的发育顺序 白三烯生成途径可在嗜酸性粒细胞生成过程中确定 通过分子、蛋白质和功能分析从脐带血中提取。最后， 日本血吸虫gp49蛋白家族基因和cDNA的克隆 小鼠优先表达的免疫球蛋白超家族 肥大细胞和巨噬细胞导致了gp49家族的定义。 以及观察到它的成员调节细胞与细胞的相互作用 激活的T细胞。这一发现，以及与此相关的cdna的分离 粘附性人单核/巨噬细胞，可以分析粘附性 Gp49家族成员在两个物种中的功能，它们的细胞谱 表达，以及按细胞/细胞和固体寻找反配体 分别用转染体和重组蛋白进行时相分析。

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.