Imatinib inhibits the functional capacity of cultured human monocytes

Andrea L. Dewar, Kathleen V. Doherty, Timothy Hughes, A. Bruce Lyons

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Imatinib is a tyrosine kinase inhibitor that has been reported to specifically inhibit the growth of bcr-abl expressing chronic myeloid leukaemia progenitors. This drug functions by blocking the ATP-binding site of the kinase domain of bcr-abl, and has also been found to inhibit the c-abl, platelet-derived growth factor receptor, ARG and stem cell factor receptor tyrosine kinases. Reports have recently emerged demonstrating that imatinib also inhibits the growth of non-malignant haemopoietic cells. Here, we demonstrate that concentrations of imatinib within the therapeutic dose range inhibit the function of cultured monocytes (CM) from normal donors. A decrease in the response of CM to LPS was observed morphologically and functionally, with CM grown in the presence of imatinib showing decreased pseudopodia formation and inhibition of IL-6 and TNF-α production following LPS stimulation. Imatinib also reduced the ability of M-CSF and GM-CSF stimulated CM to phagocytose zymosan particles, with uptake of non-opsonized zymosan by M-CSF stimulated CM (M-CM) being most affected. M-CM that had been cultured in the presence of imatinib were also impaired in their ability to stimulate responder cells in a mixed lymphocyte reaction. These results demonstrate that human monocytes cultured in the presence of imatinib are functionally impaired, and suggest that imatinib displays inhibitory activity against other kinase(s) that play a role in monocyte/macrophage development.

Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalImmunology and Cell Biology
Volume83
Issue number1
DOIs
Publication statusPublished or Issued - 1 Feb 2005
Externally publishedYes

Keywords

  • Function
  • Imatinib
  • Macrophage
  • Monocyte
  • STI-571

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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