Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization.


AIMS: Monocyte systemic levels are known to be a major determinant of ischaemic tissue revascularization, but the mechanisms mediating mobilization of different monocyte subsets-Ly6C(hi) and Ly6C(lo)-to the blood and their respective role in post-ischaemic neovascularization are not clearly understood. Here, we hypothesized that distinct chemokine/chemokine receptor pathways, namely CCL2/CCR2, CX3CL1/CX3CR1, and CCL5/CCR5, differentially control monocyte subset systemic levels, and might thus impact post-ischaemic vessel growth. METHODS AND RESULTS: In a model of murine hindlimb ischaemia, both Ly6C(hi) and Ly6C(lo) monocyte circulating levels were increased after femoral artery ligation. CCL2/CCR2 activation enhanced blood Ly6C(hi) and Ly6C(lo) monocyte counts, although the opposite effect was seen in mice with CCL2 or CCR2 deficiency. CX3CL1/CX3CR1 strongly impacted Ly6C(lo) monocyte levels, whereas CCL5/CCR5 had no role. Only CCL2/CCR2 signalling influenced neovascularization, which was increased in mice overexpressing CCL2, whereas it markedly decreased in CCL2-/- mice. Moreover, adoptive transfer of Ly6C(hi)-but not Ly6C(lo)-monocytes enhanced vessel growth and blood flow recovery. CONCLUSION: Altogether, our data demonstrate that regulation of proangiogenic Ly6C(hi) monocytes systemic levels by CCL2/CCR2 controls post-ischaemic vessel growth, whereas Ly6C(lo) monocytes have no major role in this setting.

Authors: Cochain C, Rodero MP, Vilar J, Récalde A, Richart AL, Loinard C, Zouggari Y, Guérin C, Duriez M, Combadière B, Poupel L, Lévy BI, Mallat Z, Combadière C, Silvestre JS
Journal: Cardiovasc. Res.; 2010 Oct 01; 88(1) 186-95. doi:10.1093/cvr/cvq153
Year: 2010
PubMed: PMID: 20501509 (Go to PubMed)