Published online before print November 8, 2007, doi: 10.1161/CIRCRESAHA.107.160697
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 27, 2007
Revised on October 16, 2007
Accepted on October 30, 2007
Protective Role of CXC Receptor 4/CXC Ligand 12 Unveils the Importance of Neutrophils in Atherosclerosis
Alma Zernecke ;
From the Institute for Molecular Cardiovascular Research (A.Z., Y.D.T., E.S., K.B., S.M., R.K., C.W.), Institute of Pathology (J.B.), and Medical Clinic III (F.T.), Rheinisch-Westfälische Technische Hochschule, Aachen University, Germany; Division of Biopharmaceutics (I.B., E.A.B.), Gorlaeus Laboratories, Leiden University, The Netherlands; Medical Policlinic (A.S.), and Institute of Physiology (M.S.), Ludwig-Maximilians-University, Munich, Germany; and Department of Physiology (O.S.), Karolinska Institute, Stockholm, Sweden.
* To whom correspondence should be addressed. E-mail: cweber{at}ukaachen.de.
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
Key words: atherosclerosis • cardiovascular disease • chemokines • leukocytes • vascular inflammation
Related Article:
- Open Sesame!: CXCR4 Blockade Recruits Neutrophils Into the Plaque
- Julie Sainz and Masataka Sata
Circ. Res. 2008 102: 154-156.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  J. Duchene, C. Cayla, S. Vessillier, R. Scotland, K. Yamashiro, F. Lecomte, I. Syed, P. Vo, A. Marrelli, C. Pitzalis, et al. Laminar Shear Stress Regulates Endothelial Kinin B1 Receptor Expression and Function: Potential Implication in Atherogenesis Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1757 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Irvine, M. R. Andrews, M. A. Fernandez-Rojo, K. Schroder, C. J. Burns, S. Su, A. F. Wilks, R. G. Parton, D. A. Hume, and M. J. Sweet Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages J. Leukoc. Biol., February 1, 2009; 85(2): 278 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zernecke, E. Shagdarsuren, and C. Weber Chemokines in Atherosclerosis: An Update Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1897 - 1908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Spyridopoulos, S. Fichtlscherer, R. Popp, S. W. Toennes, B. Fisslthaler, T. Trepels, A. Zernecke, E. A. Liehn, C. Weber, A. M. Zeiher, et al. Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1967 - 1974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Quinn, M. Henriques, T. Parker, A. S. Slutsky, and H. Zhang Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1817 - H1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yvan-Charvet, C. Welch, T. A. Pagler, M. Ranalletta, M. Lamkanfi, S. Han, M. Ishibashi, R. Li, N. Wang, and A. R. Tall Increased Inflammatory Gene Expression in ABC Transporter-Deficient Macrophages: Free Cholesterol Accumulation, Increased Signaling via Toll-Like Receptors, and Neutrophil Infiltration of Atherosclerotic Lesions Circulation, October 28, 2008; 118(18): 1837 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Soehnlein, A. Zernecke, E. E. Eriksson, A. G. Rothfuchs, C. T. Pham, H. Herwald, K. Bidzhekov, M. E. Rottenberg, C. Weber, and L. Lindbom Neutrophil secretion products pave the way for inflammatory monocytes Blood, August 15, 2008; 112(4): 1461 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Nemenoff, P. A. Simpson, S. B. Furgeson, N. Kaplan-Albuquerque, J. Crossno, P. J. Garl, J. Cooper, and M. C.M. Weiser-Evans Targeted Deletion of PTEN in Smooth Muscle Cells Results in Vascular Remodeling and Recruitment of Progenitor Cells Through Induction of Stromal Cell-Derived Factor-1{alpha} Circ. Res., May 9, 2008; 102(9): 1036 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Brand-Herrmann Where Do We Go for Atherothrombotic Disease Genetics? Stroke, April 1, 2008; 39(4): 1070 - 1075. [Full Text] [PDF]
|
|
|
|
|
|
J. Sainz and M. Sata Open Sesame!: CXCR4 Blockade Recruits Neutrophils Into the Plaque Circ. Res., February 1, 2008; 102(2): 154 - 156. [Full Text] [PDF]
|
|