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STI571 inhibits growth and adhesion of human mast cells in culture
Author(s) -
Takeuchi Kouichi,
Koike Kenichi,
Kamijo Takehiko,
Ishida Shuichi,
Nakazawa Yozo,
Kurokawa Yumi,
Sakashita Kazuo,
Kinoshita Tatsuya,
Matsuzawa Shigeyuki,
Shiohara Masaaki,
Yamashita Tetsuji,
Nakajima Motowo,
Komiyama Atsushi
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0602284
Subject(s) - stem cell factor , biology , mast cell , fibronectin , tyrosine phosphorylation , microbiology and biotechnology , cell adhesion , interleukin 33 , cell growth , immunology , haematopoiesis , cell , cytokine , stem cell , phosphorylation , biochemistry , interleukin , extracellular matrix
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.