The hemopoietic system is regulated by an array of hemopoietic factors or hemopoietins, which directly controls the differentiation, growth and maturation of hemopoietic cells. Among these hemopoietins are the colony stimulating factors (CSF's) which regulate myelopoiesis and induces granulocyte/macrophage (G/M) colony formation in vitro. Responsiveness to CSF's is genetically regulated. Autoimmune prone NZB mice fail to respond to G-CSF. Murine mast cells proliferate in vitro in the presence of mast cell growth factor (MCGF). NZB mice, likewise, fail to respond to MCGF. As MCGF has been reported to be closely related or identical to a pluripotent stem cell stimulating factor, it is of great interest and importance to further evaluate the genetic control of responsiveness to these hemopoietic factors using NZB as a model. Experiments designed to determine the number of genes involved, how defects are expressed and whether these defects can be corrected will be conducted. Natural killer (NK) cells have been implicated to play an active role in defense against nascent tumors. Moreover, natural killer cells have been demonstrated to inhibit in vitro GM-CSF formation, and evidence suggests that large granular lymphocytes, of which NK cells constitute a subpopulation, are active producers of CSF's. Thus, proposal is made to analyze further the role of NK cells in hematopoiesis. Studies will involve defining the conditions for generating NK cells from Dexter type long-term marrow cultures (LMC), characterizing NK precursors in LMC, determining the role of NK cells in hemopoiesis in LMC making use of mouse strains with genetically determined high and low NK levels. Neurotransmitters have been reported to affect cells of the immune system including NK cells. It is of interest to determine if these agents also influence hemopoiesis using in vitro colony assays and LMC. Finally, the ability of human mast cells to proliferate in vitro in suspension culture will be explored, and the existence of a human active MCGF determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
1R01AM034740-01
Application #
3153354
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065