Abstract
Communication within the hematopoietic-neuroendocrine-immune axis is partly mediated by neurotransmitters (e.g. substance P, SP) and cytokines. SP mediates neuromodulation partly through the stimulation of bone marrow (BM) progenitors. This study shows that SP, through the neurokinin-1 receptor, stimulates the proliferation of primitive hematopoietic progenitors: cobblestone-forming cells (CAFC, CD34+). This effect is optimal when macrophage is included within the fibroblast support. Indirect induction of IL-1 could be important in the proliferation of CAFC colonies by SP. Phenotypic and functional studies suggest that SP might directly interact with the CD34+/CD45(dim) population. These studies indicate that SP can initiate a cascade of biological responses in the BM stroma and stem cells to stimulate hematopoiesis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cell Division / drug effects
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Cell Division / immunology
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Cells, Cultured
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Drug Synergism
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Fluorouracil / pharmacology
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Gene Expression / immunology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / immunology*
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Humans
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Immunosuppressive Agents / pharmacology
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Interleukin-1 / immunology
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Interleukin-3 / pharmacology
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Interleukin-6 / pharmacology
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Macrophages / cytology
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Macrophages / immunology
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Neuroimmunomodulation / physiology
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RNA, Messenger / analysis
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Receptors, Interleukin-1 / genetics
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Receptors, Neurokinin-1 / genetics
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Receptors, Neurokinin-2 / genetics
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Stem Cell Factor / pharmacology
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Stromal Cells / cytology*
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Stromal Cells / immunology*
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Substance P / pharmacology*
Substances
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Immunosuppressive Agents
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Interleukin-1
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Interleukin-3
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Interleukin-6
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RNA, Messenger
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Receptors, Interleukin-1
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Receptors, Neurokinin-1
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Receptors, Neurokinin-2
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Stem Cell Factor
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Substance P
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Fluorouracil