Recipient HO-1 inducibility is essential for posttransplant hepatic HO-1 expression and graft protection: From bench-to-bedside.
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol 19, iss 2, 2019
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academicJournal
Zugriff:
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 (18hour), were transplanted to syngeneic myeloid HO-1 deficient (mHO-1 KO) or FLOX (control) hosts, and sampled postreperfusion (6hour). 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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Recipient HO-1 inducibility is essential for posttransplant hepatic HO-1 expression and graft protection: From bench-to-bedside.
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol 19, iss 2, 2019 |
Veröffentlichung: | eScholarship, University of California, 2019 |
Medientyp: | academicJournal |
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