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Gastroenterology. 2003 Mar;124(3):692-700.

ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.

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1
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.

Abstract

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.

PMID:
12612908
DOI:
10.1053/gast.2003.50098
[Indexed for MEDLINE]
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