Induction of Mast Cell Proliferation, Maturation, and Heparin Synthesis by the Rat c-Kit Ligand, Stem Cell Factor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-07, Vol.88 (14), p.6382-6386
• Main Authors: Tsai, Mindy, Takeishi, Takashi, Thompson, Helen, Langley, Keith E., Zsebo, Krisztina M., Metcalfe, Dean D., Geissler, Edwin N., Galli, Stephen J.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; AMINES; ANIMAL CELLS; ANIMALS; ANTICOAGULANTS; AZOLES; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOCHEMISTRY; Biological and medical sciences; BIOSYNTHESIS; CARBOHYDRATES; Cell Division - drug effects; Cell growth; Cell lines; Cell physiology; CELL PROLIFERATION; Cells, Cultured; CHEMISTRY; CONNECTIVE TISSUE CELLS; CYTOCHEMISTRY; Cytokines; DAYS LIVING RADIOISOTOPES; Developmental biology; DRUGS; EVEN-ODD NUCLEI; Female; Fundamental and applied biological sciences. Psychology; HEMATOLOGIC AGENTS; Hematopoietic Cell Growth Factors - pharmacology; HEPARIN; Heparin - biosynthesis; HETEROCYCLIC COMPOUNDS; HISTAMINE; Histamines; IMIDAZOLES; ISOTOPES; Kinetics; LABELLED COMPOUNDS; LIGANDS; LIGHT NUCLEI; MAMMALS; MAST CELLS; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - physiology; MICE; Mice, Inbred Strains; Molecular and cellular biology; MUCOPOLYSACCHARIDES; NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; POLYSACCHARIDES; RADIOISOTOPES; Rats; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; RODENTS; SACCHARIDES; Skin - cytology; Skin - drug effects; Skin Physiological Phenomena; SOMATIC CELLS; Stem Cell Factor; Sulfates; SULFUR 35; SULFUR ISOTOPES; SYNTHESIS; UPTAKE; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.14.6382

We investigated the effects of a newly recognized multifunctional growth factor, the c-kit ligand stem cell factor (SCF), on mouse mast cell proliferation and phenotype. Recombinant rat SCF164(rrSCF164) induced the development of large numbers of dermal mast cells in normal mice in vivo. Many of these mast cells had features of "connective tissue-type mast cells" (CTMC), in that they were reactive both with the heparin-binding fluorescent dye berberine sulfate and with safranin. In vitro, rrSCF164induced the proliferation of cloned interleukin 3 (IL-3)-dependent mouse mast cells and primary populations of IL-3-dependent, bone marrow-derived cultured mast cells (BMCMC), which represent immature mast cells, and purified peritoneal mast cells, which represent a type of mature CTMC. BMCMC maintained in rrSCF164not only proliferated but also matured. Prior to exposure to rrSCF164, the BMCMC were alcian blue positive, safranin negative, and berberine sulfate negative; had a histamine content of 0.08 ± 0.02 pg per cell; and incorporated [35]sulfate into chondroitin sulfates. After 4 wk in rrSCF164, the BMCMC were predominantly safranin positive and berberine sulfate positive, had a histamine content of 2.23 ± 0.39 pg per cell, and synthesized35S-labeled proteoglycans that included substantial amounts (41-70%) of [35S]heparin. These findings identify SCF as a single cytokine that can induce immature, IL-3-dependent mast cells to mature and to acquire multiple characteristics of CTMC. These findings also directly demonstrate that SCF can regulate the development of a cellular lineage expressing c-kit through effects on both proliferation and maturation.