Extracellular calcium increases CXCR4 expression on bone marrow‐derived cells and enhances pro‐angiogenesis therapy
Open Access
- 1 September 2009
- journal article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 13 (9b), 3764-3773
- https://doi.org/10.1111/j.1582-4934.2009.00691.x
Abstract
Cell surface receptors play major roles in the mobilization and homing of progenitor cells from the bone marrow to peripheral tissues. CXCR4 is an important receptor that regulates homing of leucocytes and endothelial progenitors in response to the chemokine stromal cell-derived factor-1 (SDF-1). Ionic calcium is also known to regulate chemotaxis of selective bone marrow cells (BMCs) through the calcium-sensing receptor, CaR. Here we show that calcium regulates CXCR4 expression and BMC responses to SDF-1. CaCl2 treatment of BMC induced a time- and dose-dependent increase in both the transcription and cell surface expression of CXCR4. BMC subpopulations expressing VEGFR2+, CD34+ and cKit+/Sca-1+ were especially sensitive to calcium. The effects were blocked by calcium influx inhibitors, anti-CaR antibody and the protein synthesis inhibitor cycloheximide, but not by the CXCR4 antagonist AMD3100. Calcium treatment also enhanced SDF-1-mediated CXCR4 internalization. These changes were reflected in significantly improved chemotaxis by SDF-1, which was abolished by AMD3100 and by antibody against CXCR4. Calcium pre-treatment improved homing of CD34+ BMCs to ischemic muscle in vivo, and enhanced revascularization in ischemic mouse hindlimbs. Our results identify calcium as a positive regulator of CXCR4 expression that promotes stem cell mobilization, homing and therapy.Keywords
This publication has 47 references indexed in Scilit:
- Stromal Cell–Derived Factor-1α Confers Protection Against Myocardial Ischemia/Reperfusion InjuryCirculation, 2007
- Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factorCardiovascular Research, 2007
- Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factorBiochemical and Biophysical Research Communications, 2005
- High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cellsGrowth Factors, 2005
- Up‐regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP‐responsive elementThe FASEB Journal, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Roles of PLC-β2 and -β3 and PI3Kγ in Chemoattractant-Mediated Signal TransductionScience, 2000
- Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar developmentNature, 1998
- The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tractNature, 1998
- Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1Nature, 1996