Long-term objective of the proposed research is to elucidate the roles of Fc gamma receptors (Fc gamma R) in the regulation of functions of cells which participate in the immune response. In this proposal, efforts will be focused on the biochemical and biological properties of Fc gamma Rs present on the surface of murine macrophage surface, since many of macrophage functions, such as phagocytosis of opsonized particles, killing of tumor cells, presentation of antigens, and the secretion of factors which modulate T and B cells, have been shown to require the participation of cell surface Fc gamma Rs.
Specific aims are: 1) to investigate the Fc gamma 2aR-mediated mechanism(s) of the activation of adenylate cyclase; 2) to further characterize the biochemical properties of Fc gamma 2b R protein; 3) to investigate the functional relationship between Fc gamma 2b R and the membrane adenylate cyclase system; and 4) to investigate the Fc gamma R-mediated mechanism(s) of the suppression of IFN gamma action.
These aims will be approached by: 1) biochemical characterization of Fc gamma R proteins isolated from the detergent lysate of P388D1, cells; 2) production and characterization of polyclonal and monclonal antibodies directed against the isolated Fc gamma R proteins; 3) clarification of the nature of protein kinase activities associated with IgG2a-binding proteins; 4) delineation of the relationship between Fcgamma 2bR and membrane adenylate cyclase; and 5) characterization of cAMP-dependent protein kinases which may play an essential role in the modulation of the IFN gamma action. Results obtained are expected to aid our understanding of the pathways of signal transmittance, initially triggered by Fc gamma receptors at the macrophage surface. It is also expected that the proposed studies will give us informations, useful for the understanding of the biochemical sequence of events, which follows the initial signal and leads to the regulation of macrophage function.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035977-05
Application #
3173489
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-06-01
Project End
1990-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Li, Y; Ito, N; Suzuki, T et al. (1995) Dexamethasone inhibits nitric oxide-mediated cytotoxicity via effects on both macrophages and target cells. Immunopharmacology 30:177-86
Fujihara, M; Connolly, N; Ito, N et al. (1994) Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production. J Immunol 152:1898-906
Fujihara, M; Ito, N; Pace, J L et al. (1994) Role of endogenous interferon-beta in lipopolysaccharide-triggered activation of the inducible nitric-oxide synthase gene in a mouse macrophage cell line, J774. J Biol Chem 269:12773-8
Muroi, M; Muroi, Y; Suzuki, T (1994) The binding of immobilized IgG2a to Fc gamma 2a receptor activates NF-kappa B via reactive oxygen intermediates and tumor necrosis factor-alpha 1. J Biol Chem 269:30561-8
Fujihara, M; Muroi, M; Muroi, Y et al. (1993) Mechanism of lipopolysaccharide-triggered junB activation in a mouse macrophage-like cell line (J774). J Biol Chem 268:14898-905
Muroi, M; Suzuki, T (1993) Role of protein kinase A in LPS-induced activation of NF-kappa B proteins of a mouse macrophage-like cell line, J774. Cell Signal 5:289-98
Muroi, M; Muroi, Y; Yamamoto, K et al. (1993) Influence of 3' half-site sequence of NF-kappa B motifs on the binding of lipopolysaccharide-activatable macrophage NF-kappa B proteins. J Biol Chem 268:19534-9
Suzuki, T (1991) Signal transduction mechanisms through Fc gamma receptors on the mouse macrophage surface. FASEB J 5:187-93
Novotney, M; Chang, Z L; Uchiyama, H et al. (1991) Protein kinase C in tumoricidal activation of mouse macrophage cell lines. Biochemistry 30:5597-604
Yamada, A; Suzuki, T (1989) Fc gamma 2b receptor-mediated phagocytosis by a murine macrophage-like cell line (P388D1) and peritoneal resident macrophages. Up-regulation by the inhibitors of phospholipase A2 and cyclooxygenase. J Immunol 142:2457-63

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