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Type: Journal article
Title: Imatinib inhibits the functional capacity of cultured human monocytes
Author: Dewar, A.
Doherty, K.
Hughes, T.
Lyons, A.
Citation: Immunology and Cell Biology, 2005; 83(1):48-56
Publisher: Blackwell Publishing Asia
Issue Date: 2005
ISSN: 0818-9641
Statement of
Andrea L. Dewar, Kathleen V. Doherty, Timothy P. Hughes and Bruce Lyons
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-╬▒ 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.
Keywords: imatinib; STI-571; monocyte; macrophage; function
RMID: 0020092107
DOI: 10.1111/j.1440-1711.2004.01296.x
Appears in Collections:Medicine publications

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