title: Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout mice.
abstract: OBJECTIVE
  Atypical chemokine receptor 1 (Ackr1; previously known as the Duffy antigen receptor for chemokines or Darc) is thought to regulate acute inflammatory responses in part by scavenging inflammatory CC and CXC chemokines; however, evidence for a role in chronic inflammation has been lacking. Here we investigated the role of Ackr1 in chronic inflammation, in particular in the setting of atherogenesis, using the apolipoprotein E-deficient (ApoE(-/-)) mouse model.
  
  
  RESULTS
  Ackr1(-/-)ApoE(-/-) and Ackr1(+/+)ApoE(-/-) littermates were obtained by crossing ApoE(-/-) mice and Ackr1(-/-) mice on a C57BL/6J background. Ackr1 (+/+)ApoE(-/-)mice fed a Western diet up-regulated Ackr1 expression in the aorta and had markedly increased atherosclerotic lesion size compared with Ackr1(-/-)ApoE(-/-) mice. This difference was observed in both the whole aorta and the aortic root in both early and late stages of the model. Ackr1 deficiency did not affect serum cholesterol levels or macrophage, collagen or smooth muscle cell content in atherosclerotic plaques, but significantly reduced the expression of Ccl2 and Cxcl1 in the whole aorta of ApoE(-/-) mice. In addition, Ackr1 deficiency resulted in a modest decrease in T cell subset frequency and inflammatory mononuclear phagocyte content in aorta and blood in the model.
  
  
  CONCLUSIONS
  Ackr1 deficiency appears to be protective in the ApoE knockout model of atherogenesis, but it is associated with only modest changes in cytokine and chemokine expression as well as T-cell subset frequency and inflammatory macrophage content.
authors: Molecular Signaling Section, Laboratory of Molecular Immunology (LMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: Wuzhou
authors: W
authors: Wan
authors: Molecular Signaling Section, Laboratory of Molecular Immunology (LMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: Qian
authors: Q
authors: Liu
authors: Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
authors: Michail S
authors: MS
authors: Lionakis
authors: Molecular Signaling Section, Laboratory of Molecular Immunology (LMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: Ana Paula M P
authors: AP
authors: Marino
authors: National Heart, Lung and Blood Institute (NHLBI) Animal MRI Core, NIH, Bethesda, MD, USA.
authors: Stasia A
authors: SA
authors: Anderson
authors: Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
authors: Muthulekha
authors: M
authors: Swamydas
authors: Molecular Signaling Section, Laboratory of Molecular Immunology (LMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA pmm@nih.gov.
authors: Philip M
authors: PM
authors: Murphy
mesh_terms: D000818:Animals; D005260:Female; D019264:Adoptive Transfer; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001025:Aortitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D066273:Diet, Western; D004195:Disease Models, Animal; D004375:Duffy Blood-Group System / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D004375:Duffy Blood-Group System; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse
keywords: Atherosclerosis; Chemokine receptor; Inflammation; Leukocytes