title: Monocyte chemotactic protein 3 is a homing factor for circulating angiogenic cells.
abstract: OBJECTIVE
  Circulating angiogenic cells (CAC) participate in cardiac repair. CAC recruitment to the ischaemic heart is mainly induced by the chemokine (C-X-C motif) receptor 4 (CXCR4)/stromal-cell derived factor-1α axis. However, CAC mobilization is only partly prevented by CXCR4 blockade, indicating that other mechanisms are involved. Since the expression of monocyte chemotactic protein 3 (MCP3) is increased in ischaemic hearts, we hypothesized that it may participate in CAC mobilization.
  
  
  RESULTS
  CAC were obtained from peripheral blood mononuclear cells of healthy volunteers. In vitro migration of CAC was concentration-dependently increased by recombinant MCP3 (one-fold increase, P= 0.001), and this effect was inhibited by antibodies neutralizing the chemokine (C-C motif) receptor 1 (CCR1). CCR1 expression at the surface of CAC was confirmed by flow cytometry. Conditioned medium from heparan sulfate-activated macrophages, which contained MCP3, induced the migration of CAC (one-fold increase, P= 0.01). This increase was partly inhibited by CCR1 antibodies. The migration of CAC was also stimulated by macrophage inflammatory protein 3β. This effect was blocked by CCR7 antibodies and was of lower magnitude than that of MCP3. MCP3 induced the formation of blood vessels in Matrigel plugs implanted in mice (1.5-fold increase, P< 0.001). This effect was abrogated by anti-CCR1 antibodies.
  
  
  CONCLUSIONS
  This study shows that MCP3 stimulates the migration of CAC and angiogenesis, suggesting that MCP3 may be useful to improve cardiac repair.
authors.affiliation: Laboratory of Cardiovascular Research, Centre de Recherche Public-Santé, 120 route d'Arlon, L1150 Luxembourg,  Luxembourg.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bousquenaud
authors.forename: Chantal
authors.initials: C
authors.lastname: Schwartz
authors.forename: Frédérique
authors.initials: F
authors.lastname: Léonard
authors.forename: Magali
authors.initials: M
authors.lastname: Rolland-Turner
authors.forename: Daniel
authors.initials: D
authors.lastname: Wagner
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D054410:Chemokine CCL7 / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D054410:Chemokine CCL7; D002630:Chemotactic Factors; D019402:Macrophage Inflammatory Proteins; D019718:Receptors, CXCR4; D011994:Recombinant Proteins