Stem cell factor augments tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-mediated dendritic cell hematopoiesis.
We describe the effects of stem cell factor (SCF) on the dendritic cell (DC) pathway and provide evidence for the existence of a post granulocyte-macrophage colony-forming unit (GM-CFU) DC progenitor. When employed with cytokines regulating DC development (tumor necrosis factor [TNF] + GM colony-stimulating factor [GM-CSF]), SCF increased the size of monocyte (mono) and mono-DC colonies arising from cord blood CD34+ progenitor cells. The overall plating efficiency of these colonies increased approximately threefold, as compared with growth in TNF + GM-CSF. Most (approximately 70%) of the CFUs were mono-DC CFU, and SCF did not alter the proportion of mono-DC CFU to mono-CFU obtained with TNF + GM-CSF alone. Proliferation, as measured by thymidine uptake and manual cell counts, at least doubled and occurred earlier (by day 4). In long-term cultures established with TNF + GM-CSF + SCF, high levels of proliferation were prolonged for up to three weeks. These were associated with extended DC development and the capacity to form 2 degree mono-DC colonies. There was no induction of polymorphonuclear (PMN) cells in 2 degree cultures treated with either GM-CSF, GM-CSF + SCF or GM-CSF + granulocyte CSF (G-CSF), implying that the DC progenitor being replated was post GM-CFU. DC progeny arising in the presence of SCF exhibited typical DC features including: the lack of nonspecific esterase and phagocytic activity, the presence of class II major histocompatibility complex (MHC) antigens, the absence of CD14 antigens, and the ability to induce a potent mixed leukocyte reaction. Thus, SCF augments DC growth from progenitor cells without altering the developmental commitment instituted by TNF + GM-CSF. This enhancement follows the same general mechanisms previously reported for SCF-mediated lineage enhancement, i.e., increased colony size, number and plating capacity.
Santiago-Schwarz
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Division of Rheumatology, Allergy & Immunology, Winthrop University Hospital, Mineola, New York, USA.
Rappa
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Laky
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Carsons
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D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D007959:Lymphocyte Culture Test, Mixed; D009077:Mucins / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D009077:Mucins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor