Abstract

The objective of the proposed investigations is to gain a better understanding of phagocytic cell function in normals and in patients with hematologic disorders. We plan to elucidate the events that are responsible for the activation activity and inactivation of the oxidase system that is involved in the bacteriocidal and tumoricidal activity of phagocytic cells. We will examine ligand binding, calcium translocation, membrane depolarization, membrane fluidity, whole cell superoxide production and activity of the NAD(P)H oxidase responsible for it. We will also examine the ontogeny of the oxidase and myeloperoxidase responsible for it. We will also examine the ontogeny of the oxidase and myeloperoxidase and the role of oxidative metabolism in the monoclonal antibody dependent cell mediated cytotoxicity of lymphoid cells and tumor cells. We will also attempt to label and isolate the NAD(P)H oxidase system using a photoaffinity labelled FAD. These studies in normal and deficient cells will help define the biochemical and biophysical events necessary for phagocytic cells to function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019656-04
Application #
3129010
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Voter, K Z; Whitin, J C; Torres, A et al. (2001) Ozone exposure and the production of reactive oxygen species by bronchoalveolar cells in humans. Inhal Toxicol 13:465-83
Eskenazi, A E; Pinkas, J; Whitin, J C et al. (1993) Role of antioxidant enzymes in the induction of increased experimental metastasis by hydroxyurea. J Natl Cancer Inst 85:711-21
Gibson-Berry, K L; Whitin, J C; Cohen, H J (1993) Modulation of the respiratory burst in human neutrophils by isoproterenol and dibutyryl cyclic AMP. J Neuroimmunol 43:59-68
Davis, J M; Whitin, J (1992) Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation. J Appl Physiol 72:1320-5
Novak, M J; Cohen, H J (1991) Depolarization of polymorphonuclear leukocytes by Porphyromonas (Bacteroides) gingivalis 381 in the absence of respiratory burst activation. Infect Immun 59:3134-42
Liang, S L; Woodlock, T J; Whitin, J C et al. (1990) Signal transduction in N-formyl-methionyl-leucyl-phenylalanine and concanavalin A stimulated human neutrophils: superoxide production without a rise in intracellular free calcium. J Cell Physiol 145:295-302
Whitin, J C; Takahashi, K; Cohen, H J (1987) Activation of neutrophil superoxide production by concanavalin A can occur at low levels of intracellular ionized calcium. Blood 69:762-8
Cohen, H J; Tape, E H; Novak, J et al. (1987) The role of glutathione reductase in maintaining human granulocyte function and sensitivity to exogenous H2O2. Blood 69:493-500
Takahashi, K; Avissar, N; Whitin, J et al. (1987) Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme. Arch Biochem Biophys 256:677-86
Takahashi, K; Cohen, H J (1986) Selenium-dependent glutathione peroxidase protein and activity: immunological investigations on cellular and plasma enzymes. Blood 68:640-5

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