Allograft immune response with sCR1 intervention.
The deposition of complement (C) components on tissues of transplanted organs may induce many proinflammatory responses. The role of such C activation in allograft rejection is uncertain. We addressed this question by inhibiting C at the level of the C3 and C5 convertases, preventing C activation and progression of its cascade, using recombinant human soluble complement receptor 1 (sCR1) in an unsensitized rat renal allograft model. Fully MHC disparate Lewis to DA rat renal allograft recipients given 25 mg/kg sCR1 daily, with saline-treated allograft recipients as controls (n = 15 in each group), were sacrificed from day 1 to day 5 post-transplant, and examined histopathologically, and for the deposition of C3 and C5b-9 membrane attack complex (MAC), and for the presence of leucocyte antigen markers. Treated animals demonstrated a reduction in vascular injury and cellular infiltration, coincident with reduced C deposition. Flow cytometric analysis of leucocyte subpopulations in the spleen showed a reduction in activated (CD25 positive) B and T cells in treated animals, compared to saline treated controls. The results suggest that C inhibition with sCR1, in an unsensitized model of allograft rejection, was able to suppress the vascular and cell mediated components of tissue injury. The data support not only a role for C in antibody and possibly cell mediated cytotoxicity in the graft, but also suggest a role in the primary immune response leading to both T cell and B cell activation.
Pratt
J R
JR
Department of Renal Medicine, Guy's Hospital, London, UK.
Hibbs
M J
MJ
Laver
A J
AJ
Smith
R A
RA
Sacks
S H
SH
D000818:Animals; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011951:Receptors, Complement / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology
D011951:Receptors, Complement; D011994:Recombinant Proteins; C082885:soluble complement inhibitor 1