Journal
ATHEROSCLEROSIS
Volume 214, Issue 2, Pages 316-324Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.11.023
Keywords
Macrophage phenotypic heterogeneity; M-CSF; GM-CSF; Atherosclerosis; Microarrays; Tissue microarrays
Funding
- Institut National de la Sante Et de la Recherche Medicale (France)
- Fondation pour la Recherche Medicale (France) [FDT20070910166]
- Institut de l'Atherothrombose (France)
- EU (Switzerland) [201668]
- SNF (Switzerland) [310030-118245]
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Objectives: We characterized the transcriptional profiles of GM-CSF- (GM-MO) and M-CSF-induced macrophages (M-MO) and investigated in situ a subset of differentially expressed genes in human and mouse atherosclerotic lesions. Methods and results: Using microarrays we identified a number of genes and biological processes differentially regulated in M-MO vs GM-MO. By varying in culture the M-CSF/GM-CSF ratio (0-10), a spectrum of macrophage phenotypes was explored by RT-QPCR. M-CSF (10 ng/ml) stimulated expression of several genes, including selenoprotein-1 (SEPP1), stabilin-1 (STAB1) and CD163 molecule-like-1 (CD163L1) which was inhibited by a low dose of GM-CSF (1 ng/ml); M-CSF inhibited the expression of pro-platelet basic protein (PPBP) induced by GM-CSF. Combining Tissue Microarrays/quantitative immunohistochemistry of human aortic lesions with RT-QPCR expression data either from human carotids vs mammary non-atherosclerotic arteries or from the apoE null mice normal and atherosclerotic aortas showed that, STAB1, SEPP1 and CD163L1 (M-CSF-sensitive genes) and PPBP (GM-CSF-sensitive gene) were expressed in both human arterial and apoE null mice atherosclerotic tissues. Conclusion: A balance between M-CSF vs GM-CSF defines macrophage functional polarisation and may contribute to the progression of atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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