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Recipient HO-1 inducibility is essential for posttransplant hepatic HO-1 expression and graft protection: From bench-to-bedside.
Kageyama, Shoichi; Hirao, Hirofumi; Nakamura, Kojiro; Ke, Bibo; Zhang, Min; Ito, Takahiro; Aziz, Antony; Oncel, Damla; Kaldas, Fady M; Busuttil, Ronald W; Sosa, Rebecca A; Reed, Elaine F; Araujo, Jesus A; Kupiec-Weglinski, Jerzy W.
Afiliação
  • Kageyama S; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Hirao H; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Nakamura K; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Ke B; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Zhang M; Division of Cardiology, Department of Medicine, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Ito T; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Aziz A; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Oncel D; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Kaldas FM; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Busuttil RW; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Sosa RA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Reed EF; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Araujo JA; Division of Cardiology, Department of Medicine, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
  • Kupiec-Weglinski JW; Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
Am J Transplant ; 19(2): 356-367, 2019 02.
Article em En | MEDLINE | ID: mdl-30059195
ABSTRACT
By documenting potent antioxidative and anti-inflammatory functions, preclinical studies encourage heme oxygenase-1 (HO-1)-inducing regimens in clinical orthotopic liver transplantation (OLT). We aimed to determine the importance of recipient-derived HO-1 in murine and human OLTs. Hepatic biopsies from 51 OLT patients were screened for HO-1 expression (Western blots) prior to put-in (basal) and post reperfusion (stressed) and correlated with the hepatocellular function. In parallel, livers from HO-1 proficient mice (WT; C57/BL6), subjected to ex vivo cold storage (18 hour), were transplanted to syngeneic myeloid HO-1 deficient (mHO-1 KO) or FLOX (control) hosts, and sampled postreperfusion (6 hour). In human OLT, posttransplant but not pretransplant HO-1 expression correlated negatively with ALT levels (P = .0178). High posttransplant but not pretransplant HO-1 expression trended with improved OLT survival. Compared with controls, livers transplanted into mHO-1 KO recipient mice had decreased HO-1 levels, exacerbated hepatic damage/frequency of TUNEL+ cells, increased mRNA levels coding for TNFα/CXCL1/CXCL2/CXCL10, higher frequency of Ly6G+/4HN+ neutrophils; and enhanced MPO activity. Peritoneal neutrophils from mHO-1 KO mice exhibited higher CellRox+ ratio and increased TNFα/CXCL1/CXCL2/CXCL10 expression. By demonstrating the importance of posttransplant recipient HO-1 phenotype in hepatic macrophage/neutrophil regulation and function, this translational study identifies recipient HO-1 inducibility as a novel biomarker of ischemic stress resistance in OLT.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Fígado / Heme Oxigenase-1 / Fígado / Macrófagos / Neutrófilos Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Fígado / Heme Oxigenase-1 / Fígado / Macrófagos / Neutrófilos Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article