STI571 inhibits growth and adhesion of human mast cells in culture

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...

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Bibliographic Details
Published in:Journal of leukocyte biology 2003-12, Vol.74 (6), p.1026-1034
Main Authors: 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
Format: Article
Language:English
Subjects:
Antigens, CD - metabolism
Apoptosis - drug effects
Benzamides
CD34+ cells
Cell Adhesion - drug effects
Cell Division - drug effects
Cells, Cultured
cord blood
c‐kit
Drug Combinations
Enzyme Inhibitors - pharmacology
Female
Fetal Blood - drug effects
Fetal Blood - metabolism
Fibronectins - pharmacology
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Imatinib Mesylate
Infant, Newborn
Mast Cells - cytology
Mast Cells - metabolism
Phosphorylation
Piperazines - pharmacology
Protein-Tyrosine Kinases - antagonists & inhibitors
Proto-Oncogene Proteins c-kit - metabolism
Pyrimidines - pharmacology
stem cell factor
Tyrosine - metabolism
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Summary: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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0602284