Complement-mediated inflammation and injury in brain dead organ donors. (April 2017)

• Record Type: Journal Article
• Authors: Poppelaars, Felix; Seelen, Marc A.
• Is Part Of: Molecular immunology. Volume 84(2017:Apr.)
• Page Start: 77
• Page End: 83
• Publication Date: 2017-04
• Subjects: ACTH adrenocorticotropic hormone -- ADH anti-diuretic hormone -- AP alternative pathway -- BD brain dead/brain death -- C1-INH C1 esterase inhibitor -- CD59 membrane attack complex-inhibitory protein -- CP classical pathway -- CR1 complement receptor 1 -- CR2 complement receptor 2 -- DAMPs damage-associated molecular patterns -- DCD deceased cardiac death -- IgG immunoglobulin G -- IgM immunoglobulin M -- IL-6 interleukin 6 -- IL-1beta interleukin 1beta -- KIM-1 kidney injury marker 1 -- LP lectin pathway -- LPS lipopolysaccharide -- MBL mannose-binding lectin -- MAC membrane attack complex -- PAMPs pathogen-associated molecular patterns -- sC5b-9 soluble C5b-9 -- T3 triiodothyronine -- TGF-beta tumor growth factor beta; Complement activation -- Transplantation -- Donor brain death; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.11.004
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: During brain death, both local and systemic complement is activated in the donor. Complement activation in brain death is associated with allograft function and outcome after transplantation. Complement inhibition in the BD donor reduces inflammation and injury, thus improving graft function after transplantation. Abstract: The importance of the complement system in renal ischemia-reperfusion injury and acute rejection is widely recognized, however its contribution to the pathogenesis of tissue damage in the donor remains underexposed. Brain-dead (BD) organ donors are still the primary source of organs for transplantation. Brain death is characterized by hemodynamic changes, hormonal dysregulation, and immunological activation. Recently, the complement system has been shown to be involved. In BD organ donors, complement is activated systemically and locally and is an important mediator of inflammation and graft injury. Furthermore, complement activation can be used as a clinical marker for the prediction of graft function after transplantation. Experimental models of BD have shown that inhibition of the complement cascade is a successful method to reduce inflammation and injury of donor grafts, thereby improving graft function and survival after transplantation. Consequently, complement-targeted therapeutics in BD organ donors form a new opportunity to improve organ quality for transplantation. Future studies should further elucidate the mechanism responsible for complement activation in BD organ donors.