DIFFERENT TYPES OF HUMAN MAST CELLS

人类肥大细胞，即刻超敏反应的效应者 潜在的先天免疫，被分为两个表型 根据它们分泌颗粒中的蛋白酶组成。MCTC 细胞含有类胰蛋白酶、糜酶、组织蛋白酶G和肥大细胞 羧基肽酶；MCT细胞只含有类胰蛋白酶。干细胞因子是 人类肥大细胞的主要分化因子。参与其中 人类疾病中肥大细胞的数量和类型取决于肥大细胞的数量和类型 细胞的招募，以及它们的激活状态和存活。海流 提案涉及肥大细胞生物学的基本方面，这些方面与 这些因素。 目的研究人肥大细胞的发育和存活。糜酶 将在MCT细胞中检测mRNA的表达和潜在的诱导。 新近认识的IL-4诱导肥大细胞凋亡的能力， 并探讨IL-6对这一过程的调控作用。新技术 允许肥大细胞从单个细胞发育将被利用来 检测肥大细胞的前体细胞频率和增殖能力 祖先。神经节苷脂GD3在肥大细胞发育中的作用 接受检查。 目的2探索三种可能的调节人类活动的途径 肥大细胞。GD3参与FcepsilonR1介导的激活将 要下定决心。腺苷，已知可增强FcepsilonR1介导的 人类肥大细胞的脱颗粒，被假设通过一种 腺苷2b受体。FimH，一种甘露糖苷结合成分 肠杆菌菌毛，将被检测其激活能力 人类肥大细胞。 目标3将试图通过强迫肥大细胞使人类肥大细胞永生 表达端粒酶的祖细胞。这种逆转录酶维持 端粒，保持细胞增殖活性，防止细胞 衰老。永生化桅杆的表型和功能特征 我们将描述细胞系的特征。更好地了解肥大细胞 人类的发育和激活将提供更精确的 了解他们与人类疾病的关系，并更好地 治疗干预的策略。

Human mast cells, effectors of immediate hypersensitivity and potentially of innate immunity, have been classified into two phenotypes based on the protease composition of their secretory granules. MCTc cells contain tryptase, chymase, cathepsin G and mast cell carboxypeptidase; MCT cells contain only tryptase. Stem cell factor is the major differentiation factor for human mast cells. The involvement of mast cells in human disease depends on the numbers and types of mast cells recruited, and their activation status and survival. The current proposal addresses fundamental aspects of mast cell biology that relate to these factors. Aim I examines the development and survival of human mast cells. Chymase mRNA expression and potential induction will be examined in MCT cells. The newly-appreciated ability of IL-4 to induce apoptosis in mast cells, and of IL-6 to modulate this process will be explored. New technology allowing mast cells to develop from single cells will be exploited to examine the precursor frequency and proliferative potential of mast cell progenitors. The role of ganglioside GD3 in mast cell development will be examined. Aim 2 explores three potential pathways to modulate activation of human mast cells. GD3 involvement in FcepsilonR1- mediated activation will be determined. Adenosine, known to augment FcepsilonR1-mediated degranulation of human mast cells, is hypothesized to act through an adenosine 2b receptor. FimH, a mannoside-binding component on enterobacterial fimbria, will be examined for its ability to activate human mast cells. Aim 3 will attempt to immortalize human mast cells by forcing mast cell progenitors to express telomerase. This reverse transcriptase maintains telomeres, preserves cell proliferative activity and prevents cell senescence. Phenotypic and functional features of immortalized mast cell lines will be characterized. A better understanding of mast cell development and activation in humans will provide a more precise understanding of their involvement in human disease, and better strategies for therapeutic interventions.