Evaluation of angiopoietins and cell-derived microparticles after stem cell transplantation.
Although stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy, it involves certain serious transplant-related complications such as graft-versus-host disease (GVHD). Angiopoietins play important roles in angiogenesis. However, the role of angiopoietins after SCT is poorly understood. In this study, 52 patients underwent SCT; 26 patients received allogeneic SCT, while the remaining 26 received autologous SCT. In 48 of 52 patients, levels of angiopoietins, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay. Soluble Fas ligand (sFasL) and endothelial cell-derived microparticle (EDMP) exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and sIL-2 receptor (sIL-2R), which are GVHD markers after allogeneic SCT was observed. The level of angiopoietin (Ang)-2 in allogeneic SCT continued to increase for up to 4 weeks, although the level of Ang-1 did not show significant changes. The patients with high Ang-2 exhibited significant increase of sFasL and EDMP compared with those with low Ang-2. In addition, the patients with high-grade GVHD exhibited a significant increase in Ang-2 compared to patients with low-grade GVHD. In the in vitro experiment using endothelial cells, the suppressive effect of Ang-1 on EDMP generation by TNF-alpha was partially inhibited by the addition of Ang-2. Furthermore, multivariate regression analysis showed that EDMP and sFasL were significant factors in Ang-2 elevation. Our results suggest that Ang-2 generation after allogeneic SCT relates to GVHD.
Nomura
Shosaku
S
Division of Hematology, Kishiwada City Hospital, Osaka, Japan. shosaku-n@mbp.ocn.ne.jp
Ishii
Kazuyoshi
K
Inami
Norihito
N
Kimura
Yutaka
Y
Uoshima
Nobuhiko
N
Ishida
Hiroyuki
H
Yoshihara
Takao
T
Urase
Fumiaki
F
Maeda
Yasuhiro
Y
Hayashi
Kunio
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D002478:Cells, Cultured; D002648:Child; D042783:Endothelial Cells / Q000166:cytology*; D053222:Fas Ligand Protein / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000009:adverse effects*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D053222:Fas Ligand Protein