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.
