The research described in this proposal is based upon the new and unexpected finding that mouse nerve growth factor (NGF) is a potent granulocyte colony-stimulating factor (G-CSF) both for human and mouse granulocyte progenitor cells. The subunit of mouse nerve growth factor responsible for this unusual effect is a serine-class proteolytic enzyme, but surprisingly its protease activity is not required for the G-CSF effect.
Specific aims of this research include dissection of the chemical structure of the NGF subunit to define the protein structural components involved in its G-CSF activity; studies on the possible role of NGF in inducing differentiation both of mouse and human leukemia cell lines in culture; studies on the action of specific antibodies to NGF upon normal and leukemic bone marrow populations; and studies to determine whether other important biological enzymes (related structurally to NGF) possess multiple biologic activities unrelated to their protease activity. The present availability of NGF in virtually unlimited quantities should be of considerable value in the pursuit of studies on normal and abnormal myeloid cell growth and development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA028110-07A1
Application #
3167996
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1979-09-30
Project End
1989-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Boyle, M D; Chiodo, V A; Lawman, M J et al. (1987) Urokinase: a chemotactic factor for polymorphonuclear leukocytes in vivo. J Immunol 139:169-74
Faulmann, E L; Young, M; Boyle, M D (1987) Inactivation of the proteolytic activity of mouse nerve growth factor by human C1(activated)-inhibitor. J Immunol 138:4336-40
Saboori, A M; Young, M (1986) Nerve growth factor: biosynthetic products of the mouse salivary glands. Characterization of stable high molecular weight and 32,000-dalton nerve growth factors. Biochemistry 25:5565-71
Lawman, M J; Boyle, M D; Gee, A P et al. (1985) Nerve growth factor accelerates the early cellular events associated with wound healing. Exp Mol Pathol 43:274-81
Young, M; Gee, A P; Boyle, M D et al. (1985) Nerve growth factor. A structural relationship between its proteolytic and leukocyte-chemotactic active sites. Mol Cell Biochem 66:65-9
Boyle, M D; Lawman, M J; Gee, A P et al. (1985) Nerve growth factor: a chemotactic factor for polymorphonuclear leukocytes in vivo. J Immunol 134:564-8