The contribution of terminal complement components to acute and hyperacute allograft rejection in the rat.
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 C6 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 hyperacutely 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. Immunofluorescence demonstrated deposition of IgM, IgG and C3 in ACI allografts in PVG (C-) as well as in PVG (C+) recipients. Deposition of C6 was only found in grafts rejected by PVG (C+). The significantly longer survival of ACI cardiac allografts in C6-deficient PVG (C-) rats indicates that the membrane attack complex contributes to acute as well as antibody-mediated hyperacute allograft rejection.
Brauer
R B
RB
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2191.
Baldwin
W M
WM
Ibrahim
S
S
Sanfilippo
F
F
D000208:Acute Disease; D000818:Animals; D000906:Antibodies; D003167:Complement Activation / Q000276:immunology*; D003183:Complement C6 / Q000172:deficiency*; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology; D007114:Immunization; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D003183:Complement C6; D015938:Complement Membrane Attack Complex; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II