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

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

doi:10.2119/2005-00028.potteaux

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-gamma 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.

Highlights

METHODSChemokines play key roles in the maturation, homing, and activation of leukocytes at sites of inflammation [1]
We examined the direct role of blood-borne CCR1 in the development and composition of atherosclerotic plaques in low-density lipoprotein receptor-deficient (LDLr–/–) mice
After 12 weeks of atherogenic diet, we found an unexpected 70% increase in the extent of surface area stained with oil red O in thoracic aortas of CCR1–/– mice compared with controls (16.86 ± 2.91% vs. 9.89 ± 0.98%, respectively, P < 0.05) (Figure 2)

Summary

Introduction

METHODSChemokines play key roles in the maturation, homing, and activation of leukocytes at sites of inflammation [1]. We examined the direct role of blood-borne CCR1 in the development and composition of atherosclerotic plaques in low-density lipoprotein receptor-deficient (LDLr–/–) mice.

Results

Conclusion