Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell Factor/kit-ligand in long-term culture
Abstract
In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.
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Over 90% of SM cases harbor the KIT D816V variant, which leads to constitutive activation of receptor tyrosine kinase CD117, responsible for MC survival, proliferation, and differentiation.
“Over 90% of SM cases harbor the KIT D816V variant, that leads to the constitutive activation of the receptor tyrosine kinase CD117, on turn responsible for MC survival, proliferation, and differentiation (37, 38).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [37]
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- Authors
- Valent, P., Spanblochl, E., Sperr, W., Sillaber, C., Zsebo, K., Agis, H., Strobl, H., Geissler, K., Bettelheim, P., & Lechner, K.
- Affiliations
- University of Vienna (AT)
- Department of Internal Medicine, University of Vienna, Austria.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1992-11-01
- Volume
- 80
- Issue
- 9
- Pages
- 2237-2245
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2296776321
- Cited by
- 439
- References
- 73
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 7
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- mast cell differentiation, stem cell factor, human mast cells, bone marrow mononuclear cells, peripheral blood mononuclear cells, tryptase, histamine release, IgE receptor, basophils, cytokines, long-term culture, tissue mast cells, mast cell precursors, interleukin-3, IL-4, IL-9
- MeSH terms
- Antibodies, Monoclonal, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Hematopoietic Stem Cells, Humans, Interleukin-3, Kinetics, Mast Cells, Monocytes, Nerve Growth Factors, Recombinant Proteins, Time Factors, Antigens, CD, Interleukin-4, Macrophage Colony-Stimulating Factor, Cytokines, Hematopoietic Cell Growth Factors, Stem Cell Factor
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