Macrophage plasticity in experimental atherosclerosis.
As in human disease, macrophages (MØ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model.We found that bone marrow-derived MØ 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 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I(+) (M2) MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II(+) (M1) MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ 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 MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ 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 MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.
Khallou-Laschet
Jamila
J
UMRS698 INSERM, Paris, France.
Varthaman
Aditi
A
Fornasa
Giulia
G
Compain
Caroline
C
Gaston
Anh-Thu
AT
Clement
Marc
M
Dussiot
Michaël
M
Levillain
Olivier
O
Graff-Dubois
Stéphanie
S
Nicoletti
Antonino
A
Caligiuri
Giuseppina
G
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology*; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D001057:Apolipoproteins E; D017077:Culture Media, Conditioned