title: Bβ(15-42) attenuates the effect of ischemia-reperfusion injury in renal transplantation.
abstract: Renal ischemia-reperfusion contributes to reduced renal allograft survival. The peptide Bβ(15-42), a breakdown product of fibrin, attenuates inflammation induced by ischemia-reperfusion in the heart by competitively blocking the binding of leukocytes to endothelial VE-cadherin, but whether it could improve outcomes in renal transplantation is unknown. Here, we tested the ability of Bβ(15-42) to ameliorate the effects of renal ischemic injury during allogenic kidney transplantation in mice. In our renal transplantation model (C57BL/6 into BALB/c mice), treatment with Bβ(15-42) at the time of allograft reperfusion resulted in significantly improved survival of recipients during the 28-day follow-up (60% versus 10%). Bβ(15-42) treatment decreased leukocyte infiltration, expression of endothelial adhesion molecules, and proinflammatory cytokines. Treatment significantly attenuated allogenic T cell activation and reduced cellular rejection. Moreover, Bβ(15-42) significantly reduced tubular epithelial damage and apoptosis, which we reproduced in vitro. These data suggest that Bβ(15-42) may have therapeutic potential in transplant surgery by protecting grafts from ischemia-reperfusion injury.
authors.affiliation: Department of Nephrology and Hypertension, Medical School Hannover, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Sörensen
authors.forename: Song
authors.initials: S
authors.lastname: Rong
authors.forename: Nathan
authors.initials: N
authors.lastname: Susnik
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
authors.forename: Nelli
authors.initials: N
authors.lastname: Shushakova
authors.forename: Melanie
authors.initials: M
authors.lastname: Albrecht
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Dittrich
authors.forename: Sibylle
authors.initials: S
authors.lastname: von Vietinghoff
authors.forename: Jan Ulrich
authors.initials: JU
authors.lastname: Becker
authors.forename: Anette
authors.initials: A
authors.lastname: Melk
authors.forename: Andrea
authors.initials: A
authors.lastname: Bohlmann
authors.forename: Sonja
authors.initials: S
authors.lastname: Reingruber
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitt
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D007684:Kidney Tubules / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000187:drug effects; D014184:Transplantation, Homologous
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42)