Skip to main content

Advertisement

Log in

Soluble vascular endothelial growth factor (VEGF) receptor-1 inhibits migration of human monocytic THP-1 cells in response to VEGF

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

We aimed to investigate the regulation and contribution of vascular endothelial growth factor (VEGF) and sFlt-1(1–3) to human monocytic THP-1 migration.

Materials and methods

Ad-sFlt-1/FLAG, a recombinant adenovirus carrying the human sFlt-1(1–3) (the first three extracellular domains of FLT-1, the hVEGF receptor-1) gene, was constructed. L929 cells were infected with Ad-sFlt-1/FLAG and the expression of sFlt-1 was detected by immunofluorescent assay and ELISA. Corning® Transwell® Filter Inserts containing polyethylene terephthalate (PET) membranes with pore sizes of 3 μm were used as an experimental model to simulate THP-1 migration. Five VEGF concentrations (0, 0.1, 1, 10 and 100 ng/ml), four concentrations of sFlt-1(1–3)/FLAG expression supernatants (0.1, 1, 10 and 100 ng/ml), and monocyte chemoattractant protein-1 (MCP-1, 10 ng/ml) were used to test the ability of THP-1 cells to migrate through PET membranes.

Results

The sFlt-1(1–3) gene was successfully recombined into Ad-sFlt-1/FLAG. sFlt-1(1–3) was expressed in L929 cells transfected with Ad-sFlt-1/FLAG. THP-1 cell migration increased with increasing concentrations of VEGF, while cell migration decreased with increasing concentrations of sFlt1(1–3)/FLAG. sFlt1(1–3)/FLAG had no effect on MCP-1-induced cell migration.

Conclusions

This study demonstrated that VEGF is able to elicit a migratory response in THP-1 cells, and that sFlt-1(1–3) is an effective inhibitor of THP-1 migration towards VEGF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:938–52.

    Article  PubMed  CAS  Google Scholar 

  2. Brück W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol. 2005;252(Suppl 5):v3–9.

    Article  PubMed  Google Scholar 

  3. Frohman EM, Racke MK, Raine CS. Multiple sclerosis—the plaque and its pathogenesis. N Engl J Med. 2006;354:942–55.

    Article  PubMed  CAS  Google Scholar 

  4. Imitola J, Chitnis T, Khoury SJ. Insights into the molecular pathogenesis of progression in multiple sclerosis: potential implications for future therapies. Arch Neurol. 2006;63:25–33.

    Article  PubMed  Google Scholar 

  5. Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med. 1990;172:1025–33.

    Article  PubMed  CAS  Google Scholar 

  6. Huitinga I, Damoiseaux JG, Döpp EA, Dijkstra CD. Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats. Eur J Immunol. 1993;23:709–15.

    Article  PubMed  CAS  Google Scholar 

  7. Proescholdt MA, Jacobson S, Tresser N, Oldfield EH, Merrill MJ. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J Neuropathol Exp Neurol. 2002;61:914–25.

    PubMed  CAS  Google Scholar 

  8. Graumann U, Reynolds R, Steck AJ, Schaeren-Wiemers N. Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult. Brain Pathol. 2003;13:554–73.

    Article  PubMed  CAS  Google Scholar 

  9. Kirk SL, Karlik SJ. VEGF and vascular changes in chronic neuroinflammation. J Autoimmun. 2003;21:353–63.

    Article  PubMed  CAS  Google Scholar 

  10. Su JJ, Osoegawa M, Matsuoka T, Minohara M, Tanaka M, Ishizu T, et al. Upregulation of vascular growth factors in multiple sclerosis: correlation with MRI findings. J Neurol Sci. 2006;243:21–30.

    Article  PubMed  CAS  Google Scholar 

  11. Marumo T, Schini-Kerth VB, Busse R. Vascular endothelial growth factor activates nuclear factor-kappaB and induces monocyte chemoattractant protein-1 in bovine retinal endothelial cells. Diabetes. 1999;48:1131–7.

    Article  PubMed  CAS  Google Scholar 

  12. Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marmé D. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood. 1996;87:3336–43.

    PubMed  CAS  Google Scholar 

  13. Kim I, Moon SO, Kim SH, Kim HJ, Koh YS, Koh GY. Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem. 2001;276:7614–20.

    Article  PubMed  CAS  Google Scholar 

  14. Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, et al. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990;5:519–24.

    PubMed  CAS  Google Scholar 

  15. Kondo K, Hiratsuka S, Subbalakshmi E, Matsushime H, Shibuya M. Genomic organization of the flt-1 gene encoding for vascular endothelial growth factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors. Gene. 1998;208:297–305.

    Article  PubMed  CAS  Google Scholar 

  16. Kendall RL, Wang G, Thomas KA. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun. 1996;226:324–8.

    Article  PubMed  CAS  Google Scholar 

  17. Barleon B, Totzke F, Herzog C, Blanke S, Kremmer E, Siemeister G, et al. Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1. J Biol Chem. 1997;272:10382–8.

    Article  PubMed  CAS  Google Scholar 

  18. Ye C, Feng C, Wang S, Wang KZ, Huang N, Liu X, et al. sFlt-1 gene therapy of follicular thyroid carcinoma. Endocrinology. 2004;145:817–22.

    Article  PubMed  CAS  Google Scholar 

  19. Proescholdt MA, Heiss JD, Walbridge S, Mühlhauser J, Capogrossi MC, Oldfield EH, et al. Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain. J Neuropathol Exp Neurol. 1999;58:613–27.

    Article  PubMed  CAS  Google Scholar 

  20. Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, et al. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med. 1990;172:1535–45.

    Article  PubMed  CAS  Google Scholar 

  21. Heil M, Clauss M, Suzuki K, Buschmann IR, Willuweit A, Fischer S, et al. Vascular endothelial growth factor (VEGF) stimulates monocyte migration through endothelial monolayers via increased integrin expression. Eur J Cell Biol. 2000;79:850–7.

    Article  PubMed  CAS  Google Scholar 

  22. Reinders ME, Sho M, Izawa A, Wang P, Mukhopadhyay D, Koss KE, et al. Proinflammatory functions of vascular endothelial growth factor in alloimmunity. J Clin Invest. 2003;112:1655–65.

    PubMed  CAS  Google Scholar 

  23. Brück W, Sommermeier N, Bergmann M, Zettl U, Goebel HH, Kretzschmar HA, et al. Macrophages in multiple sclerosis. Immunobiology. 1996;195:588–600.

    PubMed  Google Scholar 

  24. Shen H, Clauss M, Ryan J, Schmidt AM, Tijburg P, Borden L, et al. Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. Blood. 1993;81:2767–73.

    PubMed  CAS  Google Scholar 

  25. Ohtani K, Egashira K, Hiasa K, Zhao Q, Kitamoto S, Ishibashi M, et al. Blockade of vascular endothelial growth factor suppresses experimental restenosis after intraluminal injury by inhibiting recruitment of monocyte lineage cells. Circulation. 2004;110:2444–52.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xueqiang Hu.

Additional information

Responsible editor: Graham Wallace.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, C., Xiong, Z., Chen, X. et al. Soluble vascular endothelial growth factor (VEGF) receptor-1 inhibits migration of human monocytic THP-1 cells in response to VEGF. Inflamm. Res. 60, 769–774 (2011). https://doi.org/10.1007/s00011-011-0332-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-011-0332-7

Keywords

Navigation