Isoquinolinesulfonamide Protein Kinase Inhibitors H7 and H8 Enhance the Effects of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) on Neutrophil Function and Inhibit GM-CSF Receptor Internalization

نویسندگان

  • Asim Khwaja
  • Mark Jones
  • Kwee Yong
  • Mervyn S. Jaswon
چکیده

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) increases neutrophil surface expression of the cellular adhesion molecule CD11 b and primes the respiratory burst stimulated by the bacterial peptide f-met-leuphe (FMLP). W e have examined the effects of the isoquinolinesulfonamide protein kinase inhibitors H7 and H8 on these functions of GM-CSF using whole blood assays. Concentrations of H7 and H8 that inhibited the 12-0tetradecanoyl-phorbol-I 3-acetate (TPA) stimulated upregulation of CD11 b expression and activation of the respiratory burst, both augmented the effects of GM-CSF. H7 and H8 enhanced the GM-CSF-stimulated increase in CD11 b expression to 21 5% k 10% (P < .05) and 233% k 45% ( P < .05), respectively, of the value obtained with GM-CSF

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تاریخ انتشار 2003