Fas ligand overexpression on allograft endothelium inhibits inflammatory cell infiltration and transplant-associated intimal hyperplasia.
Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of transplant recipients. Chronic graft vasculopathy is believed to result from recipient inflammatory responses, and it is characterized by early mononuclear cell infiltration of the transplanted vessel. Here we show that endothelial cells can be genetically modified to overexpress functional, cell-surface Fas ligand (FasL) by adenovirus-mediated gene transfer without undergoing self-destruction. In a rodent model of transplant graft vasculopathy, endothelial overexpression of FasL attenuated T cell and macrophage infiltration at 1 wk posttransplantation. These vessels also displayed reduced neointima formation at one and 2 mo posttransplantation. These results indicate that inhibition of the early inflammatory response to allografted vessels by endothelial cell-specific overexpression of FasL may have utility in the treatment of transplant arteriosclerosis.
Sata
M
M
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Luo
Z
Z
Walsh
K
K
D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D017536:Carotid Artery, Common / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics*; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*; D019014:fas Receptor / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor