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Blockade of Vascular Endothelial Growth Factor (VEGF) Aggravates the Severity of Acute Graft-versus-host Disease (GVHD) after Experimental Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

  • Kim, Ai-Ran (Department of Pediatrics, The Catholic University of Korea) ;
  • Lim, Ji-Young (Department of Pediatrics, Internal Medicine, The Catholic University of Korea) ;
  • Jeong, Dae-Chul (Department of Pediatrics, The Catholic University of Korea) ;
  • Park, Gyeong-Sin (Department of Pediatrics, Hospital Pathology, The Catholic University of Korea) ;
  • Lee, Byung-Churl (Department of Pediatrics, The Catholic University of Korea) ;
  • Min, Chang-Ki (Department of Pediatrics, Internal Medicine, The Catholic University of Korea)
  • Received : 2011.10.11
  • Accepted : 2011.11.03
  • Published : 2011.12.31
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Abstract

Background: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. Methods: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of $B6\;(H-2^b)\;{\rightarrow}B6D2F1\;(H-2^{b/d})$. Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 ($50{\mu}g/dose$) or control diluent every other day for 2 weeks (total 7 doses). Results: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor $CD3^+$ T cells on day +7 compared to control treated animals. The donor $CD4^+$ and $CD8^+$ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. Conclusion: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.

Keywords

References

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