BONE MARROW CELL ADHESION MOLECULES

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）代表一对受体-配体 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。

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.