Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes

Autor: Maik Drechsler, Robert Ryan Koenen, Yvonne Döring, Christian Weber, Christoph D. Garlichs, Esther Lutgens, Dirk Lievens, Mihail Hristov, Manuela Mandl, Helene Hartwig, Santosh Vijayan, Klaus Kemmerich, Delia Projahn, Alma Zernecke, Almudena Ortega-Gomez, Oliver Soehnlein
Přispěvatelé: Pathologie, Biochemie, RS: CARIM School for Cardiovascular Diseases, Pathology, ACS - Amsterdam Cardiovascular Sciences, AII - Amsterdam institute for Infection and Immunity, Medical Biochemistry
Jazyk: angličtina
Rok vydání: 2013
Předmět:
CCR1
Apolipoprotein E
Carotid Artery Diseases
Male
CCR2
Chemokine
Time Factors
Chemokine CXCL1
Apoptosis
030204 cardiovascular system & hematology
Monocytes
Receptors
Interleukin-8B
Chemokine receptor
Leukocyte Count
Mice
0302 clinical medicine
Macrophage
Aorta
Research Articles
Mice
Knockout
0303 health sciences
biology
Adoptive Transfer
3. Good health
Chemotaxis
Leukocyte
medicine.anatomical_structure
Carotid Arteries
monocyte
Disease Progression
Molecular Medicine
Receptors
Chemokine
Leukocyte Reduction Procedures
Signal Transduction
Receptors
CCR5
Aortic Diseases
Receptors
CCR1
Diet
High-Fat
03 medical and health sciences
Apolipoproteins E
Monocytosis
medicine
Animals
ddc:610
mobilization
030304 developmental biology
Monocyte
chemokine
medicine.disease
Atherosclerosis
Mice
Inbred C57BL
Disease Models
Animal
recruitment
Immunology
biology.protein
Zdroj: EMBO Molecular Medicine
EMBO Molecular Medicine, 5(3), 471-481. Wiley-Blackwell
EMBO molecular medicine, 5(3), 471-481. Wiley-Blackwell
Embo molecular medicine 5(3), 471-481 (2013). doi:10.1002/emmm.201201717
ISSN: 1757-4684
1757-4676
DOI: 10.1002/emmm.201201717
Popis: 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 \(CX_3CR1\) 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.
Databáze: OpenAIRE
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