title: Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes.
abstract: We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical (inflammatory/Gr1(hi) ) or non-classical (resident/Gr1(lo) ) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient (Apoe(-/-) ) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient Apoe(-/-) mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or CX3 CR1 in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. oliver.soehnlein@gmail.com
authors: Oliver
authors: O
authors: Soehnlein
authors: Maik
authors: M
authors: Drechsler
authors: Yvonne
authors: Y
authors: Döring
authors: Dirk
authors: D
authors: Lievens
authors: Helene
authors: H
authors: Hartwig
authors: Klaus
authors: K
authors: Kemmerich
authors: Almudena
authors: A
authors: Ortega-Gómez
authors: Manuela
authors: M
authors: Mandl
authors: Santosh
authors: S
authors: Vijayan
authors: Delia
authors: D
authors: Projahn
authors: Christoph D
authors: CD
authors: Garlichs
authors: Rory R
authors: RR
authors: Koenen
authors: Mihail
authors: M
authors: Hristov
authors: Esther
authors: E
authors: Lutgens
authors: Alma
authors: A
authors: Zernecke
authors: Christian
authors: C
authors: Weber
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054360:Chemokine CXCL1 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D007958:Leukocyte Count; D047589:Leukocyte Reduction Procedures; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000145:classification / Q000276:immunology* / Q000637:transplantation; D054389:Receptors, CCR1 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; C515301:Ccr1 protein, mouse; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B