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 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.
Takeuchi
Kouichi
K
Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
Koike
Kenichi
K
Kamijo
Takehiko
T
Ishida
Shuichi
S
Nakazawa
Yozo
Y
Kurokawa
Yumi
Y
Sakashita
Kazuo
K
Kinoshita
Tatsuya
T
Matsuzawa
Shigeyuki
S
Shiohara
Masaaki
M
Yamashita
Tetsuji
T
Nakajima
Motowo
M
Komiyama
Atsushi
A
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D000068877:Imatinib Mesylate; D007231:Infant, Newborn; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D001549:Benzamides; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005353:Fibronectins; D010879:Piperazines; D011743:Pyrimidines; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit