STRUCTURE AND FUNCTION OF MONOCYTE/GRANULOCYTE ANTIGENS

骨髓单核细胞从多能干细胞向成骨细胞的分化 成熟的、有功能的单核/巨噬细胞和粒细胞是有序的， 从罕见的多能干细胞开始的多步骤过程 骨髓。这一过程伴随着组织化学变化，如 以及细胞上蛋白质的出现和/或消失 浮出水面。该项目的长期目标是了解 控制髓系细胞分化的机制，以及 阐明髓系分化抗原的功能。这个项目 将首先关注CD14，这是一种膜蛋白，其表达是 诱导干细胞向成熟单核细胞分化 巨噬细胞。可溶性CD14在淋巴系和髓系中的作用 将在造血学中检查细胞分化和/或功能 单核细胞和B细胞的祖细胞测定和体外功能测定 细胞。此外，将分离出小鼠基因并用于研究 CD14在小鼠体内的功能。此外，这些DNA序列 负责调节CD14组织特异性表达的将是 利用瞬时转基因系统和转基因小鼠进行鉴定。 最后，对CD14的功能进行了分析。 接近了。CD14的表达对细胞生长、形态和功能的影响 未成熟髓系细胞的表型，通常不表达CD14， 将通过将可表达的CD14构建体导入它们来确定。 此外，CD14在转基因小鼠中异常表达的影响 将会被确定。过表达CD14的转基因小鼠将是 产生，并改变细胞的细胞性和迁移在各种 包括造血组织在内的组织将被分析。此外， 免疫球蛋白微增强子将连接到CD14基因并 将产生具有表达CD14的淋巴样细胞的转基因小鼠。 这一异常表达对造血功能的影响及临床意义 对各种组织的细胞密度进行分析。

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.