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 con- centrations 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 phosphoryla- tion of c-kit. The compound also suppressed the early phase of mast cell development. The extinc- tion of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cy- tometric 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 mole- cules. Our results may provide a fundamental in- sight for the clinical application of STI571 in al- lergic disorders. J. Leukoc. Biol. 74: 1026-1034; 2003.