Published online before print February 1, 2007, doi: 10.1161/01.RES.0000259043.42571.68
© 2007 American Heart Association, Inc.
Integrative Physiology |
Importance of CXC Chemokine Receptor 2 in the Homing of Human Peripheral Blood Endothelial Progenitor Cells to Sites of Arterial Injury
From the Institute for Molecular Cardiovascular Research (IMCAR) (M.H., A.Z., K.B., E.A.L., E.S., A.L., C.W.) and Interdisciplinary Center for Clinical Research "BIOMAT" (M.H., E.A.L., E.S., A.L., C.W.), University Hospital Aachen, Germany.
Correspondence to Dr Christian Weber, Institut für Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. E-mail cweber{at}ukaachen.de
Circulating endothelial progenitor cells (EPCs) may contribute to endothelial regeneration; however, the exact mechanisms of their arterial homing remain elusive. We examined the role of the angiogenic chemokine receptor CXCR2 in the homing of human EPCs. Isolated EPCs expressed CXCR2 together with kinase insert domain–containing receptor, CD31, vascular endothelial cadherin, and CXCR4. Adhesion assays under flow conditions showed that EPCs preferentially adhered to ß2-integrin ligands, that firm arrest on fibronectin or fibrinogen was enhanced by the CXCR2 ligands CXCL1 or CXCL7, and that blockade of CXCR2 significantly reduced EPC adhesion on platelet-coated endothelial matrix. This was corroborated by the involvement of CXCR2 in EPC recruitment to denuded areas of murine carotid arteries ex vivo and in vivo. Notably, blocking CXCR2 inhibited the incorporation of human EPCs expressing CXCR2 at sites of arterial injury in athymic nude mice. Immunoreactivity for the ß-thromboglobulin isoform CXCL7 was observed in murine platelets and denuded smooth muscle cells (SMCs) early after wire injury, and transcripts for CXCL7 and CXCL1 were detected in isolated human arterial SMCs. Human KDR+CXCR2+ cells showed better in situ adhesion to injured murine carotid arteries than KDR+CXCR2– cells, were predominantly CD14+, and improved CXCR2-dependent endothelial recovery after injury in nude mice. In conclusion, our data clearly demonstrate the importance of CXCR2 for the homing of circulating EPCs to sites of arterial injury and for endothelial recovery in vivo.
Key Words: chemokines • bone marrow • adhesion • vascular injury
This article has been cited by other articles:
 |
|
 |
|
  E. J. Suuronen, P. Zhang, D. Kuraitis, X. Cao, A. Melhuish, D. McKee, F. Li, T. G. Mesana, J. P. Veinot, and M. Ruel An acellular matrix-bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model FASEB J, May 1, 2009; 23(5): 1447 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhu, L. Zhang, M. Alexeyev, D. F. Alvarez, S. J. Strada, and T. Stevens Type 5 phosphodiesterase expression is a critical determinant of the endothelial cell angiogenic phenotype Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L220 - L228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Obi, K. Yamamoto, N. Shimizu, S. Kumagaya, T. Masumura, T. Sokabe, T. Asahara, and J. Ando Fluid shear stress induces arterial differentiation of endothelial progenitor cells J Appl Physiol, January 1, 2009; 106(1): 203 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Maeng, H.-J. Choi, J.-Y. Kwon, Y.-W. Park, K.-S. Choi, J.-K. Min, Y.-H. Kim, P.-G. Suh, K.-S. Kang, M.-H. Won, et al. Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLC{beta}2 axis Blood, January 1, 2009; 113(1): 233 - 243. [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]
|
|
|
|
|
|
C. A. Gleissner, P. von Hundelshausen, and K. Ley Platelet Chemokines in Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 1920 - 1927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Keeley, B. Mehrad, and R. M. Strieter Chemokines as Mediators of Neovascularization Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 1928 - 1936. [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]
|
|
|
|
 |
|
 A. Schober and C. Weber Leptin and EPCs in Arterial Injury: Yes, We Can! Circ. Res., August 29, 2008; 103(5): 447 - 449. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Schroeter, M. Leifheit, P. Sudholt, N.-M. Heida, C. Dellas, I. Rohm, F. Alves, M. Zientkowska, S. Rafail, M. Puls, et al. Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion Circ. Res., August 29, 2008; 103(5): 536 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu Stem Cells and Transplant Arteriosclerosis Circ. Res., May 9, 2008; 102(9): 1011 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rigamonti, C. Fontaine, B. Lefebvre, C. Duhem, P. Lefebvre, N. Marx, B. Staels, and G. Chinetti-Gbaguidi Induction of CXCR2 Receptor by Peroxisome Proliferator-Activated Receptor {gamma} in Human Macrophages Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 932 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 217 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. M. Lutgens, K. B. J. M. Cleutjens, M. J. A. P. Daemen, and S. Heeneman Cathepsin cysteine proteases in cardiovascular disease FASEB J, October 1, 2007; 21(12): 3029 - 3041. [Abstract] [Full Text] [PDF]
|
|