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-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.
Institut National de la Santé et de la Recherche Médicale, INSERM U689, Hôpital Lariboisière, Paris, France.
Stéphane
S
Potteaux
Christophe
C
Combadière
Bruno
B
Esposito
Saveria
S
Casanova
Régine
R
Merval
Patrice
P
Ardouin
Ji-Liang
JL
Gao
Philip M
PM
Murphy
Alain
A
Tedgui
Ziad
Z
Mallat
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002678:Chimera; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics
D018836:Inflammation Mediators; D054389:Receptors, CCR1; D011973:Receptors, LDL