Fas ligand overexpression on allograft endothelium inhibits inflammatory cell infiltration and transplant-associated intimal hyperplasia

J Immunol. 2001 Jun 1;166(11):6964-71. doi: 10.4049/jimmunol.166.11.6964.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta
  • Arteriosclerosis / immunology
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control
  • Carotid Artery, Common / immunology
  • Carotid Artery, Common / metabolism
  • Carotid Artery, Common / pathology
  • Carotid Artery, Common / transplantation*
  • Cell Movement / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic / genetics
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / transplantation*
  • Fas Ligand Protein
  • Gene Transfer Techniques
  • Humans
  • Hyperplasia
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Jurkat Cells
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Ligands
  • Male
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics*
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred WF
  • Transplantation, Homologous
  • Tunica Intima / immunology
  • Tunica Intima / pathology*
  • fas Receptor / genetics

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Faslg protein, rat
  • Ligands
  • Membrane Glycoproteins
  • fas Receptor