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