Journal
IMMUNOBIOLOGY
Volume 221, Issue 10, Pages 1068-1072Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2016.05.004
Keywords
Complement; Transplantation; Ischaemia reperfusion injury; Kidney; Innate immunity
Categories
Funding
- Medical Research Council [MR/L022699/1, MR/L020254/1, MR/J006742/1, MR/M012263/1, G1001141] Funding Source: researchfish
- MRC [MR/M012263/1, MR/L022699/1] Funding Source: UKRI
- Medical Research Council [G1001141, MR/J006742/1, MR/L022699/1, MR/L020254/1] Funding Source: Medline
- Department of Health Funding Source: Medline
Ask authors/readers for more resources
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. (C) 2016 Published by Elsevier GmbH.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available