Macrophage plasticity in experimental atherosclerosis

Jamila Khallou-Laschet, Aditi Varthaman, Giulia Fornasa, Caroline Compain, Anh Thu Gaston, Marc Clement, Michaël Dussiot, Olivier Levillain, Stéphanie Graff-Dubois, Antonino Nicoletti, Giuseppina Caligiuri

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Abstract

As in human disease, macrophages (M∅) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of M∅ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model. We found that bone marrow-derived M∅ submitted to M1 and M2 polarization specifically expressed arginase (Arg) II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 M∅ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I+ (M2) M∅. This type of M∅ favored the proliferation of smooth muscle cells, in vitro. Arg II+ (M1) M∅ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 M∅ phenotype. In order to address whether the M2-.M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized M∅ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg Iand Arg II-expressing M∅ also argued against a recent recruitment of M1 M∅ in the lesion. The combined data therefore suggest that the M2-.M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the M∅ infiltrate towards the M2 phenotype may exert an atheroprotective action. Copyright:

Original languageEnglish
Article numbere8852
JournalPLoS One
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 25 2010

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Khallou-Laschet, J., Varthaman, A., Fornasa, G., Compain, C., Gaston, A. T., Clement, M., Dussiot, M., Levillain, O., Graff-Dubois, S., Nicoletti, A., & Caligiuri, G. (2010). Macrophage plasticity in experimental atherosclerosis. PLoS One, 5(1), [e8852]. https://doi.org/10.1371/journal.pone.0008852