1. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis
- Author
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Svenja Meiler, Frank Tacke, Oliver Soehnlein, Yassin Djalali-Talab, Erik A.L. Biessen, Christian Weber, Alma Zernecke, Ilze Bot, Andreas Schober, Markus Sperandio, Kiril Bidzhekov, Regina M. Krohn, Erdenechimeg Shagdarsuren, and Jörg Bornemann
- Subjects
Chemokine ,Receptors, CXCR4 ,Neutropenia ,Physiology ,Leukocytosis ,Neutrophils ,Inflammation ,Apoptosis ,CXCR4 ,Proinflammatory cytokine ,Mice ,Apolipoproteins E ,medicine ,Animals ,CXC chemokine receptors ,Neutrophil homeostasis ,Cell Proliferation ,Mice, Knockout ,biology ,Atherosclerosis ,Chemokine CXCL12 ,Diet ,Chemotaxis, Leukocyte ,Receptors, LDL ,Immunology ,LDL receptor ,biology.protein ,medicine.symptom ,Cardiology and Cardiovascular Medicine - Abstract
The CXC ligand (CXCL)12/CXC receptor (CXCR)4 chemokine–receptor axis controls hematopoiesis, organ development, and angiogenesis, but its role in the inflammatory pathogenesis of atherosclerosis is unknown. Here we show that interference with Cxcl12/Cxcr4 by a small-molecule antagonist, genetic Cxcr4 deficiency, or lentiviral transduction with Cxcr4 degrakine in bone marrow chimeras aggravated diet-induced atherosclerosis in apolipoprotein E-deficient ( Apoe −/− ) or LDL receptor–deficient ( Ldlr −/− ) mice. Chronic blockade of Cxcr4 caused leukocytosis and an expansion of neutrophils and increased neutrophil content in plaques, associated with apoptosis and a proinflammatory phenotype. Whereas circulating neutrophils were recruited to atherosclerotic lesions, depletion of neutrophils reduced plaque formation and prevented its exacerbation after blocking Cxcr4. Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice
- Published
- 2007