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Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-122204
- 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 bloodWe 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 \(CX_3CR1\) 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.…
Author: | Oliver Soehnlein, Maik Drechsler, Yvonne Döring, Dirk Lievens, Helene Hartwig, Klaus Kemmerich, Almudena Ortega-Gómez, Manuela Mandl, Santosh Vijayan, Delia Projahn, Christoph D. Garlichs, Rory R. Koenen, Mihail Hristov, Esther Lutgens, Alma Zernecke, Christian Weber |
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URN: | urn:nbn:de:bvb:20-opus-122204 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Language: | English |
Parent Title (English): | EMBO Molecular Medicine |
ISSN: | 1757-4676 |
Year of Completion: | 2013 |
Volume: | 5 |
Pagenumber: | 471-481 |
Source: | EMBO Molecular Medicine (2013) 5, 471–481. DOI 10.1002/emmm.201201717 |
DOI: | https://doi.org/10.1002/emmm.201201717 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | CCR2; accumulation; atheriosclerotic lesions; atherosclerosis; bone-marrow; chemokine; fractalkine; hypercholeterolemia; hyperlipedemic mice; inflammatory sites; marcophages; mobilization; monocyte; recruitment; subsets |
Release Date: | 2016/02/25 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |