Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis

被引：361

作者：

Zernecke, Alma ^{[1
]}

Bot, Ilze ^{[4
]}

Djalali-Talab, Yassin ^{[1
]}

Shagdarsuren, Erdenechimeg ^{[1
]}

Bidzhekov, Kiril ^{[1
]}

Meiler, Svenja ^{[1
]}

Krohn, Regina ^{[1
]}

Schober, Andreas ^{[5
]}

Sperandio, Markus ^{[6
]}

Soehnlein, Oliver ^{[7
]}

Bornemann, Joeg ^{[2
]}

Tacke, Frank ^{[3
]}

Biessen, Erik A. ^{[4
]}

Weber, Christian ^{[1
]}

机构：

[1] Univ Aachen, Rhein Westfal TH, Inst Mol Cardiovasc Res, Aachen, Germany

[2] Univ Aachen, Rhein Westfal TH, Inst Pathol, Aachen, Germany

[3] Univ Aachen, Rhein Westfal TH, Med Clin 3, Aachen, Germany

[4] Leiden Univ, Div Biopharmaceut, Gorlaeus Labs, NL-2300 RA Leiden, Netherlands

[5] Univ Munich, Med Policlin, Munich, Germany

[6] Univ Munich, Inst Physiol, Munich, Germany

[7] Karolinska Inst, Dept Physiol, S-10401 Stockholm, Sweden

来源：

CIRCULATION RESEARCH | 2008年 / 102卷 / 02期

关键词：

atherosclerosis; cardiovascular disease; chemokines; leukocytes; vascular inflammation;

D O I：

10.1161/CIRCRESAHA.107.160697

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：209 / 217

页数：9

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