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BONE MARROW CELL ADHESION MOLECULES

骨髓细胞粘附分子

基本信息

批准号：
6373288
负责人：
Paul Wayne Kincade
金额：
$ 40.69万
依托单位：
OKLAHOMA MEDICAL RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6373288
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

项目摘要

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鉴定介导骨髓细胞之间的物理相互作用。虽然它已经很明显，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。 CD 44和透明质酸（HA）代表一个受体-配体对存在于骨髓中，它们作为一种模型被广泛研究，结构-连接关系目前的实验旨在了解CD 44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到至少有七种基质细胞产物可以与前 B细胞和它们中三种促进在 IL-7的存在。这些分子的功能意义现在正在探索和更长距离的实验应该确定更多骨髓微环境的组成部分。虽然这些基本研究集中在正常的生理过程中，可能会有对人类疾病的许多影响。例如，了解如何干细胞通常固定在骨髓中，采集它们进行移植关于干细胞如何认识到独特的骨髓内皮细胞可能会建议如何提高他们的移植。在这个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、猫免疫缺陷病毒和白喉毒素对细胞的作用。还有它们参与各种炎症过程的证据，肿瘤细胞转移、移植排斥反应和哮喘。因此，我们认为，治疗这些病症的尝试可能对骨髓的功能。