The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peripheral blood basophils

• Published in: The Journal of immunology (1950) Vol. 149; no. 2; pp. 599 - 608
• Main Authors: Columbo, M, Horowitz, EM, Botana, LM, MacGlashan, DW, Jr, Bochner, BS, Gillis, S, Zsebo, KM, Galli, SJ, Lichtenstein, LM
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.07.1992; American Association of Immunologists
• Subjects: Antibodies, Monoclonal - immunology; Basophils - drug effects; Basophils - metabolism; Biological and medical sciences; Calcium - metabolism; Cell physiology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hematopoietic Cell Growth Factors - pharmacology; Histamine Release - drug effects; Humans; Immunoglobulin E - physiology; Interleukin-3 - pharmacology; Mast Cells - drug effects; Mast Cells - metabolism; Molecular and cellular biology; Prostaglandin D2 - secretion; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - pharmacology; Proto-Oncogene Proteins c-kit; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; Skin - cytology; SRS-A - secretion; Stem Cell Factor; Human; Histamine; Immunomodulation; Ligand; C-Onc gene; Mast cell; Skin; Basophil; Release; Protooncogene; Growth factor; Biological receptor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.149.2.599

The gene product of the steel locus of the mouse represents a growth factor for murine mast cells and a ligand for the c-kit proto-oncogene receptor, a member of the tyrosine kinase receptor class of oncogenes (for review, see O. N. Witte. 1990. Cell 63:5). We have studied the effect of the human recombinant c-kit receptor ligand stem cell factor (rhSCF) on the release of inflammatory mediators from human skin mast cells and peripheral blood basophils and compared its activity to that of rhIL-3, rhSCF (1 ng/ml to 1 microgram/ml) activated the release of histamine and PGD2 from mast cells isolated from human skin. Analysis by digital video microscopy indicated that purified human skin mast cells (84 +/- 5% pure) responded to rhSCF (0.1 to 1 microgram/ml) challenge with a rapid, sustained rise in intracellular Ca2+ levels that was accompanied by secretion of histamine. A brief preincubation (10 min) of mast cells with rhSCF (0.1 pg/ml to 1 ng/ml) significantly enhanced (100 +/- 35%) the release of histamine induced by anti-IgE (3 micrograms/ml), but was much less effective on IgE-mediated release of PGD2. In contrast, a short term incubation with rhSCF did not potentiate the secretion of histamine activated by substance P (5 microM). A 24-h incubation of mast cells with rhSCF did not affect the release of mediators induced by anti-IgE (3 micrograms/ml), probably due to receptor desensitization, rhSCF (1 ng/ml to 3 micrograms/ml) neither caused release of histamine or leukotriene C4 (LTC4) release from leukocytes of 14 donors, nor induced a rise in intracellular Ca2+ levels in purified (greater than 70%) basophils. Brief preincubation (10 min) of leukocytes with rhSCF (1 ng/ml to 3 micrograms/ml) caused an enhancement (69 +/- 11%) of anti-IgE-induced release of histamine that was significant at concentrations as low as 3 ng/ml (p less than 0.05), whereas it appeared less effective in potentiating IgE-mediated LTC4 release. In contrast, a prolonged incubation (24 h) with rhSCF (0.1 pg/ml to 100 ng/ml) did not enhance the release of histamine or LTC4 induced by anti-IgE (0.1 microgram/ml), whereas rhIL-3 (3 ng/ml) significantly potentiated the release of both mediators.