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Excerpt
Hyaluronate (HA) is a polysaccharide expressed ubiquitously in the extracellular matrix and on the surface of cells including endothelial cells. One of its ligands is CD44, which is known to be involved in T cell adhesion, homing, activation and signal transduction. Recent studies have demonstrated that HA blocks lymphocyte migration in vitro and prolongs allograft survival when combined with cyclosporine in vivo. In this study we investigated the effects of HA monotherapy on acute renal allograft rejection. Adult male ACI (RT1a) rats received a Lewis (RT11) kidney transplant and both native kidneys were removed simultaneously after transplant. A low molecular weight preparation of HA (LMWHA) was administered at the indicated doses intraperitoneally for ten days. Renal allograft rejection was defined as death of the animal. Untreated recipients rejected the transplanted grafts within 9 days (8.1±1.2 days). (Figure)
In animals treated with HA (0.5, 1.0, 2.0 mg/kg) graft survival was prolonged significantly (MST = 10.6±3.9, p<0.05; 20.9±17.2, p<0.05; 26.2±19, p<0.0001). Our results demonstrate the immunomodulatory effect of LMWHA monotherapy. Evaluation of underlying mechanisms may lead to the development of novel non-toxic, non-immunogenic immunosuppressive therapies.
