BONE MARROW CELL ADHESION MOLECULES

骨髓细胞粘附分子

• 批准号: 2672151
• 负责人: Paul Wayne Kincade
• 金额: $ 37.44万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672151
• 关键词: CD44 molecule; biological signal transduction; bone marrow; cell adhesion molecules; chimeric proteins; exo alpha sialidase; glycosylation; hyaluronate; immunocytochemistry; laboratory mouse; molecular cloning; osteopontin; surface antigens; tissue /cell culture

The main objective of this project is to identify molecules which mediate physical interactions between cells in bone marrow. While it is already clear that multiple families of molecules are involved, particular functions have only been tentatively assigned to a few cell adhesion molecules. CD44 and hyaluronan (HA) represent one receptor-ligand pair present in marrow and they being extensively studied as a model for structure-junction relationships. Current experiments are aimed at learning how posttranslational modifications of CD44 influence its ability to recognize HA. A new cloning strategy was developed and used to learn that at least seven stromal cell products can interact with pre- B cells and that three of them promote clonal lymphocyte growth in the presence of IL-7. The functional significance of these molecules is now being explored and longer range experiments should identify even more components of the bone marrow microenvironment. While these basic studies focus on normal physiologic processes, there are likely to be many implications for human disease. For example, an understanding of how stem cells are normally immobilized in marrow can be helpful in harvesting them for transplantation. Knowledge of how stem cells recognize the unique endothelium of marrow may suggest ways to enhance their engraftment. Molecules being studied in this project may contribute to the attachment of poliovirus, the AIDS virus, feline immunodeficiency virus and diphtheria toxin to cells. There is also evidence for their involvement in a variety of inflammatory processes, metastasis of tumor ells, transplant rejection and asthma. Therefore , attempts to treat such conditions may have undesirable effects on function of bone marrow.

该项目的主要目标是确定介导的分子 骨髓细胞之间的物理相互作用。 虽然已经是 清楚地涉及多个分子家族，特别是 功能仅暂时分配给少数细胞粘附 分子。 CD44 和透明质酸 (HA) 代表一对受体-配体 存在于骨髓中，并且它们作为模型被广泛研究 结构-连接关系。 目前的实验目的是 了解 CD44 的翻译后修饰如何影响其 识别HA的能力。 开发并使用了一种新的克隆策略 了解至少七种基质细胞产品可以与预相互作用 B 细胞，其中三种促进克隆淋巴细胞生长 IL-7 的存在。 这些分子的功能意义现在 正在探索和更广泛的实验应该发现更多 骨髓微环境的组成部分。 虽然这些基本 研究重点是正常的生理过程，很可能 对人类疾病有许多影响。例如，了解如何 干细胞通常固定在骨髓中，有助于 收获它们用于移植。 了解干细胞如何 认识骨髓独特的内皮细胞可能会提出增强骨髓内皮细胞的方法 他们的植入。 该项目中正在研究的分子可能 有助于脊髓灰质炎病毒、艾滋病病毒、猫科动物的附着 免疫缺陷病毒和白喉毒素对细胞的影响。 还有 它们参与多种炎症过程的证据， 肿瘤细胞转移、移植排斥和哮喘。 所以 ， 治疗此类疾病的尝试可能会对患者产生不良影响 骨髓的功能。