INDUCTION OF MAST-CELL PROLIFERATION, MATURATION, AND HEPARIN SYNTHESIS BY THE RAT C-KIT LIGAND, STEM-CELL FACTOR
INDUCTION OF MAST-CELL PROLIFERATION, MATURATION, AND HEPARIN SYNTHESIS BY THE RAT C-KIT LIGAND, STEM-CELL FACTOR
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DOI：
10.1073/pnas.88.14.6382
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发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
GALLI, SJ
中科院分区：
文献类型：
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作者：
TSAI, M;TAKEISHI, T;GALLI, SJ
我们研究了一种新发现的多功能生长因子，c-kit配体干细胞因子（SCF），对小鼠肥大细胞增殖和表型的影响。重组大鼠SCF 164（rrSCF 164）在正常小鼠体内诱导大量真皮肥大细胞的发育。这些肥大细胞中的许多具有"结缔组织型肥大细胞"（CTMC）的特征，因为它们与肝素结合的荧光染料硫酸小檗碱和番红都具有反应性。在体外，rrSCF 164诱导克隆的白细胞介素3（IL-3）依赖性小鼠肥大细胞和IL-3依赖性骨髓源性培养肥大细胞（BMCMC）（代表未成熟肥大细胞）和纯化的腹膜肥大细胞（代表一种成熟CTMC）的原代群体的增殖。在rrSCF 164中维持的BMCMC不仅增殖而且成熟。在暴露于rrSCF 164之前，BMCMC为阿辛蓝阳性、番红阴性和硫酸小檗碱阴性;组胺含量为0.08 +/-0.02。pg/细胞;并将[S-35]硫酸盐掺入硫酸软骨素中。在rrSCF 164中4周后，BMCMC主要为番红阳性和硫酸小檗碱阳性，组胺含量为2.23 +/-0.39 pg/细胞，并合成S-35标记的蛋白聚糖，其中包括大量（41 - 70%）[S-35]肝素。这些发现确定SCF作为一种单一的细胞因子，可以诱导未成熟的IL-3依赖性肥大细胞成熟并获得CTMC的多种特征。这些发现也直接证明SCF可以通过对增殖和成熟的影响来调节表达c-kit的细胞谱系的发育。
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, rrSCF164 induced 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 rrSCF164 not 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 [S-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 synthesized S-35-labeled proteoglycans that included substantial amounts (41-70%) of [S-35]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.