| Hepatic Fibrosis in A Long-Term Murine Model of Sepsis. | |
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MedLine Citation:
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PMID: 22266973 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABSTRACT: Chronic sequelae of sepsis represent a major, yet underappreciated clinical problem, contributing to long-term mortality and quality-of-life impairment. In chronic liver disease, inflammation perpetuates fibrogenesis, but development of fibrosis in the post-acute phase of systemic inflammation has not been studied. Therefore, a mouse model of post-acute sequelae of sepsis was established based on polymicrobial peritonitis under antibiotic protection.Survival decreased to approximately 40% within 7 days and remained constant until day 28 (post-acute phase). In survivors, clinical recovery was observed within one week, whereas white blood cell and platelet count, as well as markers of liver injury remained elevated until day 28. Macroscopically, inflammation and abscess formation was detected in the peritoneal space and on/in the liver. Microscopically, acute-chronic inflammation with ductular proliferation, focal granuloma formation in the parenchyma and substantial hepatic fibrosis was observed. Increased numbers of potentially pathogenetic macrophages and alpha-smooth-muscle-actin positive cells, presumably activated hepatic stellate cells, were detected in the vicinity of fibrotic areas. Fibrosis was associated with the presence of elastin and an augmented production/deposition of collagens I and III. Microarray analyses revealed early activation of canonical and non-canonical pathways of hepatic stellate cell transdifferentiation.Chronic sequelae of experimental sepsis were characterized by abscess formation, persistent inflammation, as well as substantial liver injury and fibrosis, the latter associated with increased numbers of macrophages/alpha-smooth-muscle-actin-positive cells and deposition of collagens I and III. This suggests persistent activation of stellate cells, with consecutive fibrosis -a hallmark of chronic liver disease- as a result of acute life-threatening infection. |
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Authors:
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Falk A Gonnert; Elke Kunisch; Mieczyslaw Gajda; Sandro Lambeck; Martina Weber; Ralf A Claus; Michael Bauer; Raimund W Kinne |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-18 |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: - ISSN: 1540-0514 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Integrated Research and Treatment Center - Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany 2 Clinic for Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany 3 Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Jena, Germany 4 Institute of Pathology, Jena University Hospital, Jena, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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