Glycoprotein colony-stimulating factors (CSFs) have been considered, since their discovery, to be growth factors promoting myelopoiesis. However, there have been isolated reports suggesting that various CSFs can elicit alterations in the functional status of more mature cells. This project was initiated to determine if macrophage-active CSFs can influence effector and accessory functions of monocytes and/or macrophages. Results indicate that macrophage-type CSF (CSF-1) is an important regulator of the inflammatory and immunoregulatory functions of mononuclear phagocytes as well as proliferative agent. CSF-1 promotes production of Alpha/Beta interferons (IFN), interleukin-1 (IL-1) and E series prostaglandins by macrophages. Additional evidence indicates that there is a differential distribution of CSF-responsiveness within macrophage populations derived from different anatomical sites which can be further defined by phenotypic expression of class II MHC antigens (Ia). In addition, CSF responsiveness of macrophages has been found to be positively influenced by previous exposure to IFNs and negatively regulated by iron-binding ferritins which appear to specifically inhibit CSF-1 stimulation of Ia+ macrophages and progenitor cells. Extended investigations indicate that CSF-1 also augments the capacity of macrophages to stimulate antigen-dependent T cell activation and to kill yeast cells of Candida albicans in a manner that is independent of receptors for IgG and does not involve enhanced production of toxic oxygen metabolites. Lastly, a CSF-1 responsive accessory cell has been identified in marrow that appears to critically regulate not only the production rate of new monocytes but also the differentiation state of the newly derived progeny. Experiments are proposed to identify this accessory cell and define the nature of its regulatory functions. Further experiments are proposed to probe the apparent relationship between CSF-1 responsiveness, expression of Ia antigen and ferritin inhabitability and, additionally, to determine if immune augmentation elicited by CSF-1 is restricted to IL-1 production or may also include augmented processing and/or presentation of antigen. Enhanced killing of Candida albicans will be further investigated with regard to endogenous intermediary signals and to any effect of CSF-1 on the expression of receptors for yeast mannans. Lastly, CSFs from EL-4 thymoma cells and P388D1 macrophage cells will be compared with CSF-1 from fibroblasts (L929) for their relative efficiencies in stimulating functional activities of macrophages.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacteriology and Mycology Subcommittee 1 (BM)
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University of Tennessee Knoxville
Schools of Arts and Sciences
United States
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Kreisberg, R; Detrick, M S; Osmand, A P et al. (1993) Cytokine mediation of the suppressive effect of ferritin on colony-stimulating factor-1-dependent monocytopoiesis. J Immunol 150:5094-103
Coker 3rd, L A; Mercadal, C M; Rouse, B T et al. (1992) Differential effects of CD4+ and CD8+ cells in acute, systemic murine candidosis. J Leukoc Biol 51:305-6
Detrick, M S; Kreisberg, R; Koontz, J W et al. (1992) Nanomolar cyclic adenosine and guanosine monophosphates stimulate macrophage colony-stimulating factor responsiveness by murine transitional progenitors. J Leukoc Biol 52:249-54
Moore, R N; Duma, E M; Bowersock, T L (1990) Bradykinin sensitization of colony-stimulating factor-1-responsive murine marrow progenitors to prostaglandin E. A property of the amino-terminal tetrapeptide fragment. J Immunol 144:667-70
Moore, R N; Osmand, A P; Dunn, J A et al. (1989) Neurotensin regulation of macrophage colony-stimulating factor-stimulated in vitro myelopoiesis. J Immunol 142:2689-94
Moore, R N; Osmand, A P; Dunn, J A et al. (1988) Substance P augmentation of CSF-1-stimulated in vitro myelopoiesis. A two-signal progenitor restricted, tuftsin-like effect. J Immunol 141:2699-703
Duma, E M; Foster, J S; Moore, R N (1988) Bradykinin sensitization of CSF-1-responsive murine mononuclear phagocyte precursors to prostaglandin E. J Immunol 141:3186-9
Foster, J S; Moore, R N (1987) Dynorphin and related opioid peptides enhance tumoricidal activity mediated by murine peritoneal macrophages. J Leukoc Biol 42:171-4
Karbassi, A; Becker, J M; Foster, J S et al. (1987) Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors. J Immunol 139:417-21
Horohov, D W; Moore, R N; Rouse, B T (1987) The regulation of herpes simplex virus-specific CTL induction by suppressor cells. Viral Immunol 1:55-68

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