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| Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells - In vivo neovascularization induced by stromal-derived factor-1 alpha |
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| Author(s): Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OMZ, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ |
| Source: AMERICAN JOURNAL OF PATHOLOGY Volume: 154 Issue: 4 Pages: 1125-1135 Published: APR 1999 |
| Times Cited: 244 References: 40 |
| Abstract: Furthermore, subcutaneous SDF-1 alpha injections into mice induced formation of local small blood vessels that was accompanied by leukocytic infiltrates. To test whether these effects were dependent on circulating leukocytes, we successfully obtained SDF-1 alpha-induced neovascularization from cross sections of leukocyte-free rat aorta. Taken together, our data indicate that SDF-1 alpha acts as a potent chemoattractant for endothelial cells of different origins bearing CXCR4 and is a participant in angiogenesis that is regulated at the receptor level by VEGF and bFGF, The contribution of chemokines toward angiogenesis is currently a focus of intensive investigation. Certain members of the CXC chemokine family can induce bovine capillary endothelial cell migration in vitro and corneal angiogenesis in vivo, and apparently act via binding to their receptors CXCR1 and CXCR2, We used an RNAse protection assay that permitted the simultaneous detection of mRNA for various CXC chemokine receptors in resting human umbilical vein endothelial cells (HUVECs) and detected low levels of only CXCR4 mRNA, Stimulation of HUVECs with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) up-regulated levels of only CXCR4 mRNA, CXCR4 specifically binds the chemokine stromal-derived factor-1 alpha (SDF-1 alpha), Competitive binding studies using I-125-labeled SDF-1 alpha with Scatchard analysis indicated that VEGF or bFGF induced an average number of approximately 16,600 CXCR4 molecules per endothelial cell, with a K-d = 1.23 x 10(-9) mol/L, These receptors were functional as HUVECs and human aorta endothelial cells (HAECs) migrated toward SDF-1 alpha. Although SDF-1 alpha-induced chemotaxis was inhibited by the addition of a neutralizing monoclonal CXCR4 antibody, endothelial chemotaxis toward VEGF was not altered; therefore, the angiogenic effect of VEGF is independent of SDF-1 alpha. |
| Document Type: Article |
| Language: English |
| Reprint Address: Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Bldg 560,Rm 21-89A, Frederick, MD 21702 USA |
Addresses:
1. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21702 USA
2. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA
3. SAIC Frederick, Intramural Res Support Program, Pathol Histotechnol Lab, Frederick, MD USA
4. NIDR, Cell Biol Sect, Bethesda, MD 20892 USA
5. St George Clin Sch, Dept Med, Kogarah, NSW Australia |
| Publisher: AMER SOC INVESTIGATIVE PATHOLOGY, INC, 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA |
| Subject Category: Pathology |
| IDS Number: 184MU |
| ISSN: 0002-9440 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |