|
KMID : 0923620110110060368
|
|
Immune Network
2011 Volume.11 No. 6 p.368 ~ p.375
|
|
|
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
Lim Ji-Young
Jeong Chang-Mo
Park Gyeong-Sin
Lee Byung-Churl
Min Chang- Ki
|
|
|
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-2b) →B6D2F1 (H-2b/d). Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 (50?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.
|
|
|
KEYWORD
|
|
|
Vascular endothelial growth factors (VEGF), Allogeneic hematopoietic stem cell transplantation, Acute graft- versus-host disease, VEGF blockade, dRK6
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
   
|