BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and neutropenic-induced mice were subjected to 70% hepatectomy. Three different approaches to block and/or deplete liver macrophages (Kupffer cells) were used. RESULTS: We found that liver from ICAM-1-deficient mice exhibited impaired regeneration after partial hepatectomy. This finding is associated with dramatic decrease in leukocyte recruitment and tissue TNF-alpha and IL-6 levels. All markers of hepatocyte proliferation were restored in ICAM-/- mice by injections of recombinant IL-6. Neutropenic animals and liver macrophage (Kupffer cell) depletion resulted in similar failure of regeneration with low levels of TNF-alpha and IL-6. CONCLUSIONS: The data suggest a novel pathway in which ICAM-1 binds to leukocytes after hepatectomy, triggering hepatocyte proliferation through Kupffer cell-dependent release of TNF-alpha and IL-6.
BACKGROUND & AIMS:Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and neutropenic-induced mice were subjected to 70% hepatectomy. Three different approaches to block and/or deplete liver macrophages (Kupffer cells) were used. RESULTS: We found that liver from ICAM-1-deficientmice exhibited impaired regeneration after partial hepatectomy. This finding is associated with dramatic decrease in leukocyte recruitment and tissue TNF-alpha and IL-6 levels. All markers of hepatocyte proliferation were restored in ICAM-/- mice by injections of recombinant IL-6. Neutropenic animals and liver macrophage (Kupffer cell) depletion resulted in similar failure of regeneration with low levels of TNF-alpha and IL-6. CONCLUSIONS: The data suggest a novel pathway in which ICAM-1 binds to leukocytes after hepatectomy, triggering hepatocyte proliferation through Kupffer cell-dependent release of TNF-alpha and IL-6.
Authors: Katarzyna Furrer; Andreas Rickenbacher; Yinghua Tian; Wolfram Jochum; Anne Greet Bittermann; Andres Käch; Bostjan Humar; Rolf Graf; Wolfgang Moritz; Pierre-Alain Clavien Journal: Proc Natl Acad Sci U S A Date: 2011-01-31 Impact factor: 11.205
Authors: Lindsey N Jackson; Shawn D Larson; Scott R Silva; Piotr G Rychahou; L Andy Chen; Suimin Qiu; Srinivasan Rajaraman; B Mark Evers Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-04-03 Impact factor: 4.052
Authors: Raghavendra Rao; Christopher S Graffeo; Rishabh Gulati; Mohsin Jamal; Suchithra Narayan; Constantinos P Zambirinis; Rocky Barilla; Michael Deutsch; Stephanie H Greco; Atsuo Ochi; Lena Tomkötter; Reuven Blobstein; Antonina Avanzi; Daniel M Tippens; Yisroel Gelbstein; Eliza Van Heerden; George Miller Journal: Gastroenterology Date: 2014-05-04 Impact factor: 22.682