en
Scientific article
English

Endothelial cell protection by dextran sulfate: a novel strategy to prevent acute vascular rejection in xenotransplantation

Published inAmerican journal of transplantation, vol. 4, no. 2, p. 181-187
Publication date2004
Abstract

We showed recently that low molecular weight dextran sulfate (DXS) acts as an endothelial cell (EC) protectant and prevents human complement- and NK cell-mediated cytotoxicity towards porcine cells in vitro. We therefore hypothesized that DXS, combined with cyclosporine A (CyA), could prevent acute vascular rejection (AVR) in the hamster-to-rat cardiac xenotransplantation model. Untreated, CyA-only, and DXS-only treated rats rejected their grafts within 4-5 days. Of the hearts grafted into rats receiving DXS in combination with CyA, 28% survived more than 30 days. Deposition of anti-hamster antibodies and complement was detected in long-term surviving grafts. Combined with the expression of hemoxygenase 1 (HO-1) on graft EC, these results indicate that accommodation had occurred. Complement activity was normal in rat sera after DXS injection, and while systemic inhibition of the coagulation cascade was observed 1 h after DXS injection, it was absent after 24 h. Moreover, using a fluorescein-labeled DXS (DXS-Fluo) injected 1 day after surgery, we observed a specific binding of DXS-Fluo to the xenograft endothelium. In conclusion, we show here that DXS + CyA induces long-term xenograft survival and we provide evidence that DXS might act as a local EC protectant also in vivo.

Keywords
  • Animals
  • Antibodies, Heterophile/blood
  • Cricetinae
  • Cyclosporine/therapeutic use
  • Dextran Sulfate/therapeutic use
  • Endothelium, Vascular/drug effects/transplantation
  • Graft Survival/drug effects
  • Heart Transplantation/immunology
  • Immunosuppression
  • Male
  • Mesocricetus
  • Rats
  • Rats, Inbred Lew
  • Transplantation, Heterologous/physiology
Affiliation Not a UNIGE publication
Citation (ISO format)
LAUMONIER, Thomas et al. Endothelial cell protection by dextran sulfate: a novel strategy to prevent acute vascular rejection in xenotransplantation. In: American journal of transplantation, 2004, vol. 4, n° 2, p. 181–187. doi: 10.1046/j.1600-6143.2003.00306.x
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1600-6135
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