Role of soluble tumor necrosis factor-related apoptosis-inducing ligand concentrations 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). Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) plays important roles in regulating cell death, immune response, and inflammation. However, the role of soluble TRAIL (sTRAIL) after SCT is poorly understood. In this study, 42 patients underwent SCT; 22 patients received allogeneic SCT, while the remaining 20 received autologous SCT. In these patients, levels of sTRAIL, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay (ELISA). In addition, a basic study of the generation of endothelial cell-derived microparticle (EDMP) by TNF-alpha and soluble Fas ligand (sFasL) was conducted. sFasL and EDMP exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of IL-6, TNF-alpha, and sIL-2R after allogeneic SCT was observed. EDMP also exhibited changes similar to sFasL. The patients with high sTRAIL exhibited significant decrease of sFasL and EDMP as compared with those without high sTRAIL. TNF-alpha and sFasL induced an increase in procoagulant and apoptotic markers in endothelial cells, and EDMP shedding was observed. Furthermore, sTRAIL inhibited the EDMP elevation caused by TNF-alpha and sFasL. The apoptotic markers such as sFasL and sTRAIL exhibited particular changes after SCT. Our results suggest that sTRAIL generation after allogeneic SCT relates to the prevention of GVHD.
Nomura
Shosaku
S
Division of Hematology, Kishiwada City Hospital, 1001, Kishiwada, Osaka 596-8501, Japan. shosaku-n@mbp.ocn.ne.jp
Ishii
Kazuyoshi
K
Inami
Norihito
N
Uoshima
Nobuhiko
N
Ishida
Hiroyuki
H
Yoshihara
Takao
T
Kitayama
Hitoshi
H
Hayashi
Kunio
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016207:Cytokines / Q000097:blood / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D053222:Fas Ligand Protein / Q000097:blood / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008223:Lymphoma / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D016207:Cytokines; D016228:Endothelial Growth Factors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha