STRUCTURE AND FUNCTION OF MONOCYTE/GRANULOCYTE ANTIGENS

骨髓单核细胞从多能干细胞分化为 成熟的，功能正常的单核细胞/巨噬细胞和粒细胞是一个有序的， 多步骤的过程开始于罕见的多能干细胞， 骨髓 这一过程伴随着组织化学变化， 以及细胞上蛋白质的出现和/或消失 面 本项目的长期目标是了解 控制骨髓细胞分化的机制，以及 阐明髓系分化抗原的功能。 这个项目 将首先关注CD 14，这是一种膜蛋白， 在干细胞分化为成熟单核细胞时被诱导， 巨噬细胞 可溶性CD 14在淋巴和髓系细胞中的作用 细胞分化和/或功能将在造血干细胞中检查。 单核细胞和B的祖细胞测定和体外功能测定 细胞 此外，鼠基因将被分离并用于研究 小鼠中CD 14的功能。 此外，DNA序列， 负责调节CD 14的组织特异性表达的是 使用瞬时转染系统和转基因小鼠鉴定。 最后，将使用几种分子生物学方法分析CD 14的功能。 接近。 研究了CD 14表达对人肝癌细胞生长、形态和功能的影响。 未成熟骨髓细胞的表型，其通常不表达CD 14， 将通过用可表达的CD 14构建体检测它们来确定。 此外，在转基因小鼠中，CD 14异常表达对小鼠的免疫功能的影响也是显著的。 将被确定。 过表达CD 14的转基因小鼠将被 产生，以及各种细胞中细胞结构和细胞迁移的变化， 将分析包括造血组织的组织。 此外该 免疫球蛋白微增强子将连接到CD 14基因， 将产生具有表达CD 14的淋巴细胞的转基因小鼠。 这种异常表达对造血的影响以及 将分析各种组织的细胞构成。

The differentiation of myelomonocytic cells from pluripotent stem cells to mature, functioning monocytes/macrophages and granulocytes is an orderly, multi-step process beginning from rare pluripotent stem cells present in the bone marrow. This process is accompanied by histochemical changes as well as the appearance and/or disappearance of proteins on the cell surface. The long term goal of this project is to understand the mechanisms that control the differentiation of myeloid cells, and to elucidate the functions of myeloid differentiation antigens. This project will initially focus on CD14, a membrane protein whose expression is induced upon the differentiation of stem cells to mature monocytes and macrophages. The role of soluble forms of CD14 on lymphoid and myeloid cell differentiation and/or function will be examined in hematopoietic progenitor assays and in in vitro functional assays of monocytes and B cells. Furthermore, the murine gene will be isolated and used to study the function of CD14 in mice. In addition, the DNA sequences that are responsible for regulating the tissue-specific expression of CD14 will be identified using transient transfection systems and transgenic mice. Finally, the function of CD14 will be analyzed using several molecular approaches. The effects of CD14 expression on the growth, morphology and phenotype of immature myeloid cells, which normally do not express CD14, will be determined by transfecting them with expressible CD14 constructs. In addition, the effects of abnormal expression of CD14 in transgenic mice will be determined. Transgenic mice which overexpress CD14 will be produced, and changes in cellularity and migration of cells in a variety of tissues including hematopoietic tissue will be analyzed. In addition, the immunoglobulin micro enhancer will be ligated to the CD14 gene and transgenic mice which have lymphoid cells expressing CD14 will be produced. The effects of this abnormal expression on hematopoiesis and the cellularity of various tissues will be analyzed.