The contribution of terminal complement components to acute and hyperacute allograft rejection in the rat

Robert Brauer, William M. Baldwin, Sherif Ibrahim, Fred Sanfilippo

Research output: Contribution to journalArticlepeer-review

Abstract

Acute rejection and antibody-mediated hyperacute allograft rejection are affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector functions of platelets, granulocytes, monocytes, and lymphocytes, while the formation of membrane attack complex (C5b-C9) can lead to rapid cell destruction. Therefore, we compared acute and Ab-mediated hyperacute allograft rejection in a recently described model of Cβ deficient PVG (C-) (RT1C) rats and their normal counterpart PVG (C+) (RT1C) rats. Cardiac allografts from fully MHC disparate ACI donors were heterotopically grafted into naive and skin graft sensitized PVG (C-) and PVG (C+) rats. ACI cardiac allografts were rejected acutely (8.3±2 days; n=7) by naive PVG (C+) recipients, but survived significantly longer in PVG (C-) recipients (22±10 days; n=10). Presensitized PVG (C+) rats rejected ACI cardiac allografts hypcracutely in 6.1 ±2.4 hr (n=5). In contrast, ACI cardiac allografts transplanted into presensitized (PVG (C-) rats had markedly longer survival of 91±14 hr (n=5). The alloantibody responses of naive PVG (C+) and PVG (C-) recipients 7 days after cardiac allografting, and of presensitized PVG (C+) and PVG (C-) recipients at time of cardiac allografting were not significantly different as measured by flow cytometry against ACI lymphocytes. Immunofluore-cence demonstrated deposition of IgM, IgG and C3 in ACI allografts in PVG (C-) as well as in PVG (C+) recipients. Deposition of 06 was only found in grafts rejected by PVG (C+). The significantly longer survival of ACI cardiac allografts in Cβ-defícient PVG (C-) rats indicates that the membrane attack complex contributes to acute as well as antibody-mediated hyperacute allograft rejection.

Original languageEnglish (US)
Pages (from-to)288-293
Number of pages6
JournalTransplantation
Volume59
Issue number2
StatePublished - 1995

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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