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Molecular Medicine

, Volume 11, Issue 1–12, pp 16–20 | Cite as

Chemokine Receptor CCR1 Disruption in Bone Marrow Cells Enhances Atherosclerotic Lesion Development and Inflammation in Mice

  • Stéphane Potteaux
  • Christophe Combadière
  • Bruno Esposito
  • Saveria Casanova
  • Régine Merval
  • Patrice Ardouin
  • Ji-Liang Gao
  • Philip M Murphy
  • Alain Tedgui
  • Ziad Mallat
Articles

Abstract

Several chemokines or chemokine receptors are involved in atherogenesis. CCR1 is expressed by macrophages and lymphocytes, two major cell types involved in the progression of atherosclerosis, and binds to lesion-expressed ligands. We examined the direct role of the blood-borne chemokine receptor CCR1 in atherosclerosis by transplanting bone marrow cells from either CCR1+/+ or CCR1−/− mice into low-density lipoprotein-receptor (LDLr)-deficient mice. After exposure to an atherogenic diet for 8 weeks, no differences in fatty streak size or composition were detected between the 2 groups. After 12 weeks of atherogenic diet, however, an unexpected 70% increase in atherosclerotic lesion size in the thoracic aorta was detected in the CCR1−/− mice, accompanied by a 37% increase in the aortic sinus lesion area. CCR1−/− mice showed enhanced basal and concanavalin A-stimulated IFN-γ production by spleen T cells and enhanced plaque inflammation. In conclusion, blood-borne CCR1 alters the immuno-inflammatory response in atherosclerosis and prevents excessive plaque growth and inflammation.

Notes

Acknowledgements

This study was supported by the “Nouvelle Société Française d’Athérosclérose” (S.P.) and the “Fondation de France” (C.C.). We are grateful to Joseph Witztum and La Jolla SCOR program (Department of Medicine, University of California San Diego, La Jolla, CA, USA) for providing EO6 antibody.

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Copyright information

© Feinstein Institute for Medical Research 2005

Authors and Affiliations

  • Stéphane Potteaux
    • 1
  • Christophe Combadière
    • 2
  • Bruno Esposito
    • 1
  • Saveria Casanova
    • 2
  • Régine Merval
    • 1
  • Patrice Ardouin
    • 3
  • Ji-Liang Gao
    • 4
  • Philip M Murphy
    • 4
  • Alain Tedgui
    • 1
  • Ziad Mallat
    • 1
  1. 1.Hôpital LariboisièreInstitut National de la Santé et de la Recherche Médicale, INSERM U689ParisFrance
  2. 2.Hôpital Pitié-SalpêtrièreINSERM U543, Laboratoire d’Immunologie Cellulaire et TissulaireParisFrance
  3. 3.Institut Gustave RoussyParisFrance
  4. 4.Laboratory of Host DefensesNational Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesdaUSA

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