DIFFERENT TYPES OF HUMAN MAST CELLS

人肥大细胞，速发型超敏反应的效应物， 潜在的先天免疫，已被分为两种表型 基于其分泌颗粒的蛋白酶组成。 MCTC 类胰蛋白酶、糜蛋白酶、组织蛋白酶G和肥大细胞 羧肽酶; MCT细胞仅含有类胰蛋白酶。干细胞因子 人肥大细胞的主要分化因子。 参与 肥大细胞在人类疾病中的作用取决于肥大细胞的数量和类型。 招募的细胞及其激活状态和存活率。 当前 提案涉及肥大细胞生物学的基本方面， 这些因素。 目的研究人肥大细胞的发育和存活。糜酶 将在MCT细胞中检查mRNA表达和潜在诱导。 IL-4诱导肥大细胞凋亡的新认识， 和IL-6调节这一过程将被探索。 新技术 允许肥大细胞从单细胞发育将被利用， 检测肥大细胞的前体频率和增殖潜力 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探讨三种可能的调节人肝细胞活化的途径。 肥大细胞 GD3参与Fc ε R1介导的激活将 被确定。 腺苷，已知可增强Fc ε R1介导的 假设人肥大细胞的脱粒作用是通过 腺苷2b受体 FimH，甘露糖苷结合组分， 肠杆菌菌毛，将检查其激活 人肥大细胞 目的3将试图通过迫使肥大细胞 祖细胞表达端粒酶。 这种逆转录酶 端粒，保持细胞增殖活性，并防止细胞 衰老 永生化肥大细胞的表型和功能特征 将表征细胞系。 对肥大细胞的认识 在人类中的发育和激活将提供一个更精确的 了解它们与人类疾病的关系， 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.