title: Mechanisms of rejection: role of complement.
abstract: OBJECTIVE
  To provide the reader with an up-to-date comprehensive review of recent findings that highlight advances describing how proteins of the complement cascades contribute to the pathogenesis of solid organ rejection. The review is focussed mainly on renal transplantation.
  
  
  RESULTS
  Of note are recent advances in elucidating the interactions between anaphylatoxins and their receptors in organ transplantation; there is evidence of direct engagement of C5aR on donor tubules and in addition, mechanisms by which the allostimulatory capacity of dendritic cells is modulated by complement are more fully understood. Activation of the lectin pathway is increasingly implicated in allograft rejection and the role of complement in modulating regulatory T cells is being vigorously investigated. As an alternative to systemic complement inhibition, there is continued focus on the design of targeted anti-complement therapies, directed to the donor organ.
  
  
  CONCLUSIONS
  Complement has evolved as the first line of defence against pathogens, employing well defined effector mechanisms to rapidly remove infectious material. However, complement effector mechanisms are also triggered during inflammation associated with solid organ transplantation. Hence, complement has a significant role in mediating donor organ injury during both the initial ischaemia/reperfusion phase and the subsequent adaptive immune responses. Research on mechanisms of complement-mediated injury in transplantation provide a basis for the development of therapies that are aimed at transiently blocking complement activation at the site of injury, whereas leaving systemic anti-bacterial complement effector mechanisms intact.
authors: Division of Transplantation Immunology & Mucosal Biology, MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, United Kingdom.
authors: Conrad A
authors: CA
authors: Farrar
authors: Steven H
authors: SH
authors: Sacks
mesh_terms: D000706:Anaphylatoxins / Q000276:immunology; D000818:Animals; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D014181:Transplantation Immunology
chemical_list: D000706:Anaphylatoxins; D003165:Complement System Proteins