Abstract

Normal blood cell formation requires the production of both positive and negative regulators of hematopoiesis. With the hematopoietic microenvironment, cell to cell interactions appear to be important for the modulation of progenitor cell proliferation and differentiation. These cellular interactions involve the production of regulators of hematopoiesis. A control cell located within the hematopoietic microenvironment is the mononuclear phagocyte. This cell, which possesses diverse functional and secretory properties, interacts with other cells of the microenvironment to produce important products involved in the regulation of hematopoiesis. Among these are interleukin 1 and tumor necrosis factor. Interleukin 1 has been shown to be involved in a number of different functions concerning the inflammatory response; while tumor necrosis factor has been implicated in tumor cytotoxicity. How do these two important monocyte products affect hematopoiesis? The proposed studies will determine whether interleukin 1 plays an integral role in the production of stimulators of early hematopoiesis by cells of the hematopoietic microenvironment and whether other monokines, such as tumor necrosis factor, or lymphokines, such as gamma interferon, are also important in the positive and negative regulation of hematopoiesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024709-03
Application #
3137885
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Guedez, L; Zucali, J (1996) Bleomycin-induced differentiation of bcl-2-transfected U937 leukemia cells. Cell Growth Differ 7:1625-31
Moreb, J S; Turner, C; Sreerama, L et al. (1995) Interleukin-1 and tumor necrosis factor alpha induce class 1 aldehyde dehydrogenase mRNA and protein in bone marrow cells. Leuk Lymphoma 20:77-84
Zucali, J R; Moreb, J; Gibbons, W et al. (1994) Radioprotection of hematopoietic stem cells by interleukin-1. Exp Hematol 22:130-5
Suresh, A; Tung, F; Moreb, J et al. (1994) Role of manganese superoxide dismutase in radioprotection using gene transfer studies. Cancer Gene Ther 1:85-90
Zucali, J R (1994) Mechanisms of protection of hematopoietic stem cells from irradiation. Leuk Lymphoma 13:27-32
Zucali, J R; Suresh, A; Tung, F et al. (1994) Cytokine protection of hematopoietic stem cells. Prog Clin Biol Res 389:207-16
Eastgate, J; Moreb, J; Nick, H S et al. (1993) A role for manganese superoxide dismutase in radioprotection of hematopoietic stem cells by interleukin-1. Blood 81:639-46
Miller, A M; Sandler, E; Kobb, S M et al. (1993) Hematopoietic growth factor induction of gamma-glutamyl transferase in the KG-1 myeloid cell line. Exp Hematol 21:9-15
Zucali, J R; Moreb, J; Bain, C (1992) Protection of cells capable of reconstituting long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide by interleukin 1 and tumor necrosis factor. Exp Hematol 20:969-73
Moreb, J; Zucali, J R; Zhang, Y et al. (1992) Role of aldehyde dehydrogenase in the protection of hematopoietic progenitor cells from 4-hydroperoxycyclophosphamide by interleukin 1 beta and tumor necrosis factor. Cancer Res 52:1770-4

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