ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell–dependent release of TNF-α/IL-6 in mice
Gastroenterology, 2003•Elsevier
Background & Aims: Tumor necrosis factor (TNF)-α 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 …
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 …
Background & Aims
Tumor necrosis factor (TNF)-α 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-α 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-α 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-α and IL-6.
Elsevier
