ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.
OBJECTIVE
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.
Selzner
Nazia
N
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Selzner
Markus
M
Odermatt
Bernhard
B
Tian
Yinghua
Y
Van Rooijen
Nico
N
Clavien
Pierre-Alain
PA
D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D007728:Kupffer Cells / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D020556:Neutrophil Infiltration / Q000502:physiology*; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1