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.
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