title: Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Paris Cardiovascular Research Center, Université Paris Descartes, UMR-S970 Paris, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Cochain
authors.forename: Mathieu P
authors.initials: MP
authors.lastname: Rodero
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Alice
authors.initials: A
authors.lastname: Récalde
authors.forename: Adèle L
authors.initials: AL
authors.lastname: Richart
authors.forename: Céline
authors.initials: C
authors.lastname: Loinard
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Zouggari
authors.forename: Coralie
authors.initials: C
authors.lastname: Guérin
authors.forename: Micheline
authors.initials: M
authors.lastname: Duriez
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadière
authors.forename: Lucie
authors.initials: L
authors.lastname: Poupel
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Lévy
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D006614:Hindlimb; D007511:Ischemia / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; C526827:Ly6 protein, mouse; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine