Effects of complement inhibition with soluble complement receptor-1 on vascular injury and inflammation during renal allograft rejection in the rat
| Autor: | Pratt, J. R., Hibbs, M. J., Laver, A. J., Smith, R. A., Sacks, S. H. |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Graft Rejection
Complement Inactivator Proteins Graft Survival Complement C3 Complement Membrane Attack Complex Kidney Transplantation Rats Receptors Complement Kinetics Solubility Ischemia Rats Inbred Lew Acute Disease Leukocytes Animals Transplantation Homologous Endothelium Vascular Research Article |
| Popis: | Complement is both an effector of the humoral immune response and a stimulator of leukocyte activation. To examine the influence of complement on the allograft response, we inhibited complement using recombinant human soluble complement receptor-1 (sCR1; TP10), in an unsensitized model of rat renal allograft rejection. Lewis to DA renal transplant recipients were treated daily with 25 mg/kg sCR1 or saline and sacrificed on days 1 to 5 after transplant. Transplanted organs were examined histologically and immunohistochemically for leukocyte subset markers and for the third component of complement, C3, and membrane attack complex deposition. A second set of recipients was followed from day 5 to day 9 to assess graft survival. sCR1-treated recipients displayed > 90% inhibition of plasma complement activity and a marked reduction in tissue C3 and membrane attack complex deposition. Inactivation of complement reduced the vascular injury such that there was almost complete sparing of vascular damage in day 5 sCR1-treated rats. There was a significant reduction in infiltrating leukocytes by day 5 after transplant, and complement inhibition delayed the time to reach a histologically defined end point of graft survival from 5 days in controls to 9 days in the sCR1-treated group. These results imply that the vascular and cell-mediated injury arises, in part, from complement activation. The partial inhibition of these injuries by sCR1 may have functional implications for strategies to inhibit allograft rejection. |
| Databáze: | OpenAIRE |
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