Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0808497 on November 12, 2008

Published online before print November 12, 2008
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Supplemental Table 1
Right arrow All Versions of this Article:
jlb.0808497v1
85/2/278    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Irvine, K. M.
Right arrow Articles by Sweet, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Irvine, K. M.
Right arrow Articles by Sweet, M. J.
(Journal of Leukocyte Biology. 2009;85:278-288.)
© 2009 Society for Leukocyte Biology

Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages

Katharine M. Irvine*, Melanie R. Andrews*, Manuel A. Fernandez-Rojo, Kate Schroder*,{dagger}, Christopher J. Burns{ddagger}, Stephen Su{ddagger}, Andrew F. Wilks{ddagger}, Robert G. Parton, David A. Hume§ and Matthew J. Sweet*,{dagger},||,¶,1

* The University of Queensland, Institute for Molecular Bioscience, Brisbane, Queensland, Australia;
{dagger} Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Queensland, Brisbane, Queensland, Australia;
{ddagger} Cytopia Pty. Ltd., Richmond, Victoria, Australia;
§ The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Scotland, United Kingdom;
|| The University of Queensland, Brisbane, School of Molecular and Microbial Sciences, Brisbane, Queensland, Australia; and
The University of Queensland, Division of Molecular Cell Biology, Institute for Molecular Bioscience, and Centre for Microscopy and Microanalysis, Brisbane, Queensland, Australia

1 Correspondence: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, 4072, Australia. E-mail: m.sweet{at}imb.uq.edu.au

M-CSF/CSF-1 supports the proliferation and differentiation of monocytes and macrophages. In mice, CSF-1 also promotes proinflammatory responses in vivo by regulating mature macrophage functions, but little is known about the acute effects of this growth factor on mature human macrophages. Here, we show that in contrast to its effects on mouse bone marrow-derived macrophages, CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF and IL-6 secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Instead, we show by expression profiling that CSF-1 modulates the HMDM transcriptome to favor a proatherogenic environment. CSF-1 induced expression of the proatherogenic chemokines CXCL10/IFN-inducible protein 10, CCL2, and CCL7 but repressed expression of the antiatherogenic chemokine receptor CXCR4. CSF-1 also up-regulated genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7, and DHCR24), and expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Consistent with these effects, CSF-1 increased levels of free cholesterol in HMDM, and the selective CSF-1R kinase inhibitor GW2580 ablated this response. These data demonstrate that CSF-1 represents a further link between inflammation and cardiovascular disease and suggest two distinct mechanisms by which CSF-1, which is known to be present in atherosclerotic lesions, may contribute to plaque progression.

Key Words: inflammation • chemokines • cholesterol