Title: Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes
Authors: Soehnlein, Oliver ×
Drechsler, Maik
Döring, Yvonne
Lievens, Dirk
Hartwig, Helene
Kemmerich, Klaus
Ortega-Gómez, Almudena
Mandl, Manuela
Vijayan, Santosh
Projahn, Delia
Garlichs, Christoph D
Koenen, Rory R
Hristov, Mihail
Lutgens, Esther
Zernecke, Alma
Weber, Christian #
Issue Date: Mar-2013
Publisher: Wiley-Blackwell Publishing Ltd.
Series Title: EMBO Molecular Medicine vol:5 issue:3 pages:471-81
Article number: 10.1002/emmm.201201717
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.
ISSN: 1757-4676
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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