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Imatinib inhibits the functional capacity of cultured human monocytes

Citation

Dewar, AL and Doherty, KV and Hughes, TP and Lyons, AB, Imatinib inhibits the functional capacity of cultured human monocytes, Immunology and Cell Biology, 83, (1) pp. 48-56. ISSN 0818-9641 (2005) [Refereed Article]

DOI: doi:10.1111/j.1440-1711.2004.01296.x

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-alpha 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

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Lyons, AB (Dr Bruce Lyons)
ID Code:73618
Year Published:2005
Web of Science® Times Cited:33
Deposited By:Medicine (Discipline)
Deposited On:2011-10-19
Last Modified:2012-03-06
Downloads:0

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