STI571 inhibits growth and adhesion of human mast cells in culture

STI571 inhibits growth and adhesion of human mast cells in culture
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STI571 抑制培养物中人类肥大细胞的生长和粘附

DOI:
10.1189/jlb.0602284
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发表时间:
2003
影响因子:
5.5
通讯作者:
A. Komiyama
A. Komiyama
中科院分区:
医学3区
文献类型:
--
作者:
K. Takeuchi;K. Koike;T. Kamijo;S. Ishida;Y. Nakazawa;Y. Kurokawa;K. Sakashita;T. Kinoshita;Shigeyuki Matsuzawa;M. Shiohara;T. Yamashita;M. Nakajima;A. Komiyama

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干细胞因子(SCF)/c-kit系统对人肥大细胞的发育至关重要。因此,我们研究了c-kit酪氨酸激酶受体抑制剂STI571对人肥大细胞增殖和功能的影响。STI571在10−、6M或更高的浓度下,通过抑制c-Kit的酪氨酸磷酸化,几乎完全取消了脐血来源的肥大细胞依赖于干细胞因子的子代。该化合物还抑制肥大细胞发育的早期阶段。根据流式细胞仪和凝胶电泳仪分析,STI571诱导肥大细胞生长的消退可能主要是由于细胞凋亡。未能影响活细胞总数的STI571暴露两小时可抑制细胞与纤维粘连蛋白的黏附,但不改变整合素分子的表达。我们的结果可能为STI571在变态反应性疾病中的临床应用提供一个基本的见解。
Stem cell factor (SCF)/c‐kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished the SCF‐dependent progeny generation from cord blood‐derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c‐kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two‐hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.
DOI: 10.1056/nejm200104053441402
发表时间: 2001-04-05
影响因子: 158.5
作者:
Druker, BJ;Sawyers, CL;Talpaz, M
通讯作者: Talpaz, M
DOI: 10.1073/pnas.96.4.1609
发表时间: 1999-02-16
影响因子: 11.1
作者:
Longley, BJ;Metcalfe, DD;Ma, YS
通讯作者: Ma, YS
Steel 因子和 c-kit 调节细胞-基质粘附。
DOI: --
发表时间: 1994
期刊: Blood
影响因子: 20.3
作者:
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通讯作者: Springer,TA