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.
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.
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DOI：
10.4049/jimmunol.149.2.599
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发表时间：
1992-07
影响因子：
4.4
通讯作者：
Michele Columbo;E. Horowitz;Luis M. Botana;D. MacGlashan;B. Bochner;S. Gillis;Krisztina M. Zsebo;Stephen J. Galli;LAWRENCEM. Lichtenstein
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作者：
Michele Columbo;E. Horowitz;Luis M. Botana;D. MacGlashan;B. Bochner;S. Gillis;Krisztina M. Zsebo;Stephen J. Galli;LAWRENCEM. Lichtenstein
小鼠steel基因座的基因产物代表鼠肥大细胞的生长因子和c-kit原癌基因受体的配体，c-kit原癌基因受体是癌基因酪氨酸激酶受体类的成员（综述参见O. N.威特1990.（《细胞》63：5）。我们研究了人重组c-kit受体配体干细胞因子（rhSCF）对人皮肤肥大细胞和外周血嗜碱性粒细胞释放炎症介质的影响，并与rhIL-3的活性进行了比较。rhSCF（1 ng/ml ~ 1 μ g/ml）激活人皮肤肥大细胞释放组胺和PGD_2。数字视频显微镜分析表明，纯化的人皮肤肥大细胞（84 +/- 5%纯）响应rhSCF（0.1至1微克/毫升）的挑战，细胞内Ca 2+水平的快速，持续上升，伴随着组胺的分泌。将肥大细胞与rhSCF（0.1 pg/ml至1 ng/ml）短暂预孵育（10 min）可显著增强（100 +/- 35%）抗IgE（3 μ g/ml）诱导的组胺释放，但对IgE介导的PGD 2释放的影响要小得多。与此相反，与rhSCF短期孵育并没有增强由P物质（5 μ M）激活的组胺的分泌。肥大细胞与rhSCF孵育24小时不影响抗IgE（3 μ g/ml）诱导的介质释放，可能是由于受体脱敏，rhSCF（1 ng/ml至3 μ g/ml）既不引起组胺释放，也不引起14名供体白细胞释放白三烯C4（LTC 4），也不诱导纯化（大于70%）嗜碱性粒细胞胞内Ca 2+水平升高。白细胞与rhSCF（1 ng/ml至3 μ g/ml）短暂预孵育（10 min）可增强（69 +/- 11%）抗IgE诱导的组胺释放，在低至3 ng/ml的浓度下具有显著性（p <0.05），而在增强IgE介导的LTC 4释放方面似乎效果较差。与此相反，与rhSCF（0.1 pg/ml至100 ng/ml）长时间孵育（24 h）并没有增强抗IgE（0.1 μ g/ml）诱导的组胺或LTC 4的释放，而rhIL-3（3 ng/ml）显着增强这两种介质的释放。（400字处截断摘要）
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.(ABSTRACT TRUNCATED AT 400 WORDS)