CHARACTERIZATION OF DIFFERENT TYPES OF HUMAN MAST CELLS

已经鉴定出两种不同类型的人类肥大细胞和 区别于主要基于中性蛋白酶的嗜碱性细胞 它们的分泌颗粒的组成。MCRC类型的主小区 含有类胰蛋白酶、类凝乳酶、类组织蛋白酶和肥大细胞 羧肽酶；MCR类型只含有类胰蛋白酶；以及嗜碱性粒细胞 含有可以忽略不计甚至检测不到的这些蛋白酶。每个单元格 类型也表现出特殊的超微结构特征和分布 在它们的宿主体内。 目的1将研究人类肥大细胞的特殊成分和 嗜碱性细胞。蛋白多糖类型(S)将与 类胰蛋白酶和糜酶蛋白及mRNA在不同类型肺癌组织中的表达 人类肥大细胞和嗜碱性粒细胞。我们预计将确定是否成熟和 发育中的MCT和mCRC细胞含有相同的蛋白多糖种类， 这些肥大细胞亚型在乳糜酶mRNA含量上是否不同，如 蛋白质含量，以及类胰蛋白酶或乳糜酶的原位杂交 MRNA在蛋白质表达前识别已承诺的肥大细胞前体细胞 并区分激活的和静止的肥大细胞，并克隆和 序列是人类嗜碱性粒细胞中一种明显独特的成分。 目标2将研究不同物种的生长、分化和存活 人类肥大细胞和嗜碱性粒细胞的类型。这些研究在一定程度上基于 重要的新发现是干细胞因子(Kit配体)是一种主要的 人类肥大细胞的生长因子。最初的重点将是IL-4， 干扰素α、伽马和各种类固醇。对Fcepsilon RI的影响 和Kit在蛋白酶和组胺上的表达，以及对MCT的选择性 将研究细胞、mCRC细胞和嗜碱性粒细胞。最后，中国的能力 小鼠和人成纤维细胞完成干细胞成熟 我们将检查依赖于因子的肥大细胞。 目标3将确定不同类型的人类肥大细胞的参与 人类疾病中的嗜碱性粒细胞，使用以前开发的技术 目标。此外，也是一种手段，通过它，肥大细胞前体频率在 可评估的外周血液将被设计并用于分析 肥大细胞增生性疾病患者的外周血象 (全身性肥大细胞增多症)、衰竭(艾滋病)和激活(过敏 鼻炎)。 肥大细胞和嗜碱性粒细胞的更好的特征将提供更多 精确的测量和监控手段。它们与人类疾病有关， 以及更好的治疗干预策略。

Two different types of human mast cells have been identified and distinguished from basophils based primarily on the neutral protease composition of their secretory granules. The MCrc type of mast cell contains tryptase, chymase, cathepsin 6-like protease and mast cell carboxypeptidase; the MCr type contains only tryptase; and basophils contain negligible to undetectable amounts of these proteases. Each cell type also exhibits special ultrastructural features and distributions within their host. Aim 1 will investigate the special constituents of human mast cells and basophils. The proteoglycan type(s) will be determined along with the expression of tryptase and chymase protein and mRNA in different types of human mast cells and basophils. We expect to determine whether mature and developing MCt and MCrc cells contain the same proteoglycan species, whether these mast cell subtypes differ in chymase mRNA content, like protein content, and whether in situ hybridization for tryptase or chymase mRNA identifies committed mast cell progenitors prior to protein expression and distinguishes activated from resting mast cells, and to clone and sequence an apparently unique constituent of human basophils. Aim 2 will examine the growth, differentiation and survival of different types of human mast cells and basophils. These studies are based in part on the important new finding that stem cell factor (Kit ligand) is a major growth factor for human mast cells. Initially the focus will be on IL-4, interferons alpha and gamma and various steroids. Effects on FcepsilonRI and Kit expression, on proteases and histamine, and selectivity for MCt cells, MCrc cells and basophils will be studied. Finally, the capacity of murine and human fibroblasts to complete the maturation of stem cell factor-dependent mast cells will be examined. Aim 3 will determine the involvement of different types of human mast cells and basophils in human diseases, using techniques developed in previous aims. Also, a means by which mast cell progenitor frequency in the peripheral blood can be assessed will be devised and used to analyze peripheral blood patients with diseases with mast cell hyperplasia (systemic mastocytosis), depletion (AIDS) and activation (allergic rhinitis). Better characterization of mast cells and basophils will provide more precise means to measure and monitor. their involvement in human disease, and better strategies for therapeutic interventions.