Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis
- PMID: 17991882
- DOI: 10.1161/CIRCRESAHA.107.160697
Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis
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.
Comment in
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Open sesame! CXCR4 blockade recruits neutrophils into the plaque.Circ Res. 2008 Feb 1;102(2):154-6. doi: 10.1161/CIRCRESAHA.107.170241. Circ Res. 2008. PMID: 18239145 Review. No abstract available.
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