| Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice. | |
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MedLine Citation:
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PMID: 20500806 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Acetaminophen (APAP) hepatotoxicity is currently the most frequent cause of acute liver failure in the US and many European countries. Although intracellular signalling mechanisms are critical for hepatocellular injury, a contribution of inflammatory cells, especially neutrophils, has been suggested. However, conflicting results were obtained when using immunological intervention strategies. AIMS: The role of neutrophils was investigated using a CD18-deficient mouse model. RESULTS: Treatment of C57Bl/6 wild type mice with 300 mg/kg APAP resulted in severe liver cell necrosis at 12 and 24 h. This injury was accompanied by formation of cytokines and chemokines and accumulation of neutrophils in the liver. However, there was no difference in the inflammatory response or liver injury in CD18-deficient mice compared with wild-type animals. In contrast to treatment with endotoxin, no upregulation of CD11b or priming for reactive oxygen was observed on neutrophils isolated from the peripheral blood or the liver after APAP administration. Furthermore, animals treated with endotoxin 3 h after APAP experienced an exaggerated inflammatory response as indicated by substantially higher cytokine and chemokine formation and twice the number of neutrophils in the liver. However, liver injury in the two-hit model was the same as with APAP alone. CONCLUSIONS: Our data do not support the hypothesis that neutrophils contribute to APAP hepatotoxicity or that a neutrophil-mediated injury phase could be provoked by a second, pro-inflammatory hit. Thus, APAP-induced liver injury in mice is dominated by intracellular mechanisms of cell death rather than by neutrophilic inflammation. |
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Authors:
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Clarence David Williams; Mary Lynn Bajt; Anwar Farhood; Hartmut Jaeschke |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Liver international : official journal of the International Association for the Study of the Liver Volume: 30 ISSN: 1478-3231 ISO Abbreviation: Liver Int. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101160857 Medline TA: Liver Int Country: England |
Other Details:
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Languages: eng Pagination: 1280-92 Citation Subset: IM |
Copyright Information:
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© 2010 John Wiley & Sons A/S. |
Affiliation:
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Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA. |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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P20 RR016475/RR/NCRR NIH HHS; P20 RR021940/RR/NCRR NIH HHS; R01 AA12916/AA/NIAAA NIH HHS; R01 DK070195/DK/NIDDK NIH HHS; T32 ES007079-26A2/ES/NIEHS NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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