title: Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis.
abstract: OBJECTIVE
  We characterized the transcriptional profiles of GM-CSF- (GM-MØ) and M-CSF-induced macrophages (M-MØ) and investigated in situ a subset of differentially expressed genes in human and mouse atherosclerotic lesions.
  
  
  RESULTS
  Using microarrays we identified a number of genes and biological processes differentially regulated in M-MØ vs GM-MØ. 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.
  
  
  CONCLUSIONS
  A balance between M-CSF vs GM-CSF defines macrophage functional polarisation and may contribute to the progression of atherosclerosis.
authors.affiliation: INSERM UMRS937, Université Pierre et Marie Curie UPMC-Paris 6, Faculté de Médecine Pierre et Marie Curie, 91 Boulevard de l'Hôpital, 75634 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brochériou
authors.forename: Seraya
authors.initials: S
authors.lastname: Maouche
authors.forename: Hervé
authors.initials: H
authors.lastname: Durand
authors.forename: Vincent
authors.initials: V
authors.lastname: Braunersreuther
authors.forename: Gilles
authors.initials: G
authors.lastname: Le Naour
authors.forename: Alexei
authors.initials: A
authors.lastname: Gratchev
authors.forename: Fabien
authors.initials: F
authors.lastname: Koskas
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Ninio
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor