The effect of locally synthesised complement on acute renal allograft rejection.
The complement system of components and receptors is one of the earliest forms of defence. Excessive or inappropriate activation can result in tissue damage, classically illustrated in immune-mediated nephritis. In addition, complement forms a bridge between innate and adaptive immunity, helping to prepare and focus T and B lymphocyte responses. More recent research in renal allograft models has shown that complement-inhibited and complement-deficient animals have reduced inflammatory injury and lowered antidonor immune responses. Furthermore, it is known that the transplanted kidney is a significant site of local synthesis of C3, although until recently the relative contribution of locally produced C3 to transplant injury was unknown. Current evidence indicates that defective local synthesis of C3 both reduces tissue injury and lowers the antidonor T cell response, substantially increasing graft survival. Among various possible explanations to account for these findings, the data favours a direct effect of complement on alloreactive T cell stimulation. Study of complement gene regulation by common immunosuppressive agents suggests that they do not influence local complement synthesis. Alternative approaches are therefore required to control the local effect of complement in the extravascular tissue compartment of the graft.
Sacks
Steven
S
Department of Nephrology and Transplantation, Guy's Hospital, King's College London, University of London, London, SE1 9RT, UK. steven.sacks@kcl.ac.uk
Zhou
Wuding
W
D000208:Acute Disease; D000818:Animals; D015932:Complement C3c / Q000096:biosynthesis / Q000276:immunology; D003181:Complement C4 / Q000096:biosynthesis / Q000276:immunology; D003165:Complement System Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D003181:Complement C4; D010446:Peptide Fragments; D015932:Complement C3c; D003165:Complement System Proteins