title: Donor brain death leads to differential immune activation in solid organs but does not accelerate ischaemia-reperfusion injury.
abstract: A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia-reperfusion injury (IRI) post-transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3(+) CD4(+) , CD3(+) CD8(+) T cells and NKp46(+) NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post-transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham-transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Paul Viktor
authors.initials: PV
authors.lastname: Ritschl
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Muhammad Imtiaz
authors.initials: MI
authors.lastname: Ashraf
authors.affiliation: Centre for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Oberhuber
authors.affiliation: Centre for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mellitzer
authors.affiliation: Centre for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Fabritius
authors.affiliation: Centre for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Resch
authors.affiliation: Centre for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ebner
authors.affiliation: Department of Molecular Pathology, University Hospital Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Department of Molecular Pathology, University Hospital Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kotsch
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001926:Brain Death / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation; D007111:Immunity, Cellular / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000209:etiology; D015427:Reperfusion Injury / Q000209:etiology* / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines
keywords: brain death; graft quality; ischaemia-reperfusion injury