Premium
ICAM‐1 UPREGULATION IN FATTY LIVERS OF ETHANOL‐TREATED DONOR MICE PROMOTES INJURY AND SINUSOIDAL LEUKOCYTE ADHERENCE AFTER TRANSPLANTATION
Author(s) -
Theruvath Tom P,
Zhong Zhi,
Ramshesh Venkat K,
Currin Robert T,
Karrasch Thomas,
Lemasters John J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1218-c
Subject(s) - immunostaining , transplantation , chemistry , medicine , downregulation and upregulation , steatosis , liver transplantation , icam 1 , endocrinology , immunohistochemistry , biochemistry , intracellular , gene
Transplantation (Tx) of alcohol (EtOH)‐induced steatotic livers causes increased graft injury. We HYPOTHESIZE that upregulation of hepatic ICAM‐1 after EtOH produces increased leukocyte adherence (stickers), resulting in injury after Tx. METHODS. C57Bl wildtype (WT) and ICAM‐1 −/− mice were gavaged with EtOH (6 g/kg) or water. Serum ALT, hepatic triglycerides and ICAM‐1 by Western blotting were assessed 12 h later. Tx of treated livers was performed into WT recipients after 12 h cold storage. After Tx, ALT, histology, 4‐hydroxynonenal (4‐HNE) immunostaining, and stickers by intravital videomicroscopy after injection of rhodamine 6G were assessed. RESULTS. EtOH gavage of WT mice increased hepatic triglycerides 10‐fold compared to water treatment (p<0.01). In WT, ICAM‐1 expression also increased but ALT was normal. At 8 h after Tx of WT grafts, ALT increased 2‐fold more with EtOH than water treatment (p<0.01), but ALT from EtOH‐treated ICAM‐1 −/− grafts was 78% less than EtOH‐treated WT (p<0.01). Necrosis and stickers were also 75% and 50% less, respectively, in EtOH‐treated ICAM‐1 −/− grafts compared to WT (p<0.05). 4‐HNE staining was equal in both fatty Tx groups. CONCLUSIONS. Increased ICAM‐1 expression in EtOH‐treated fatty livers predisposes to leukocyte adherence and disturbed microcirculation independent of oxidative stress, which leads to graft injury after Tx.