Role of the lectin complement pathway in kidney transplantation.
In the last 15 years two major advances in the role of complement in the kidney transplant have come about. The first is that ischaemia reperfusion injury and its profound effect on transplant outcome is dependent on the terminal product of complement activation, C5b-9. The second key observation relates to the function of the small biologically active fragments C3a and C5a released by complement activation in increasing antigen presentation and priming the T cell response that results in transplant rejection. In both cases local synthesis of C3 principally by the renal tubule cells plays an essential role that overshadows the role of the circulating pool of C3 generated largely by hepatocyte synthesis. More recent efforts have investigated the molecules expressed by renal tissue that can trigger complement activation. These have revealed a prominent effect of collectin-11 (CL-11), a soluble C-type lectin that is expressed in renal tissue and aligns with its major ligand L-fucose at sites of complement activation following ischaemic stress. Biochemical studies have shown that interaction between CL-11 and L-fucose results in complement activation by the lectin complement pathway, precisely targeting the innate immune response to the ischaemic tubule surface. Therapeutic approaches to reduce inflammatory and immune stimulation in ischaemic kidney have so far targeted C3 or its activation products and several are in clinical trials. The finding that lectin-fucose interaction is an important trigger of lectin pathway complement activation within the donor organ opens up further therapeutic targets where intervention could protect the donor kidney against complement.
MRC Centre for Transplantation, Division of Transplantation Immunology & Mucosal Biology, King's College London School of Medicine at Guy's, King's College and St. Thomas's Hospitals, London, United Kingdom. Electronic address: conrad.farrar@kcl.ac.uk.
Conrad A
CA
Farrar
MRC Centre for Transplantation, Division of Transplantation Immunology & Mucosal Biology, King's College London School of Medicine at Guy's, King's College and St. Thomas's Hospitals, London, United Kingdom.
Wuding
W
Zhou
MRC Centre for Transplantation, Division of Transplantation Immunology & Mucosal Biology, King's College London School of Medicine at Guy's, King's College and St. Thomas's Hospitals, London, United Kingdom.
Steven H
SH
Sacks
D000818:Animals; D015415:Biomarkers; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016030:Kidney Transplantation; D037601:Mannose-Binding Lectin / Q000276:immunology / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014181:Transplantation Immunology
D015415:Biomarkers; D037601:Mannose-Binding Lectin; D003165:Complement System Proteins
Complement; Innate immunity; Ischaemia reperfusion injury; Kidney; Transplantation