Several lines of evidence now indicate that nerve growth factor isolated from mouse salivary glands displays multiple biologic functions which span several health-related functions. These activities include: 1) activation of plasminogen; 2) promotion of the rate of wound healing; 3) neurite outgrowth stimulatory activity; 4) activation of the classical pathway of complement; and 5) chemotactic activity toward human leukocytes. The research proposal contained herein is designed to enhance our understanding of each of these potential biologic roles of NGF. Experiments are designed to further our understanding of the chemical mechanism whereby NGF undergoes autocatalytic activation - and its control by zinc ion. Studies are also presented which aim to understand the isolation of NGF from Cohn Fraction III of human serum and from bovine seminal plasma. Finally, a major goal of the laboratory is to explore and to understand our recent finding that nerve growth factor is strongly chemotactic for polymorphonuclear leukocytes and for monocytes. These studies, together with our finding that NGF can participate directly in activation of the complement system, may contribute significantly to our understanding of the role of NGF in the wound healing process.
|Young, M; Blanchard, M H; Sessions, F et al. (1988) Subunit structure of high molecular weight mouse nerve growth factor. Biochemistry 27:6675-81|
|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|