Selzner Nazia, Selzner Markus, Odermatt Bernhard, Tian Yinghua, Van Rooijen Nico, Clavien Pierre-Alain
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Gastroenterology. 2003 Mar;124(3):692-700. doi: 10.1053/gast.2003.50098.
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.
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.
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.
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.
肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6在体内介导肝细胞增殖，提示局部和全身炎症反应可能在主要组织损伤后触发肝再生。
对野生型、细胞间黏附分子（ICAM）-1基因敲除型和中性粒细胞减少诱导型小鼠进行70%肝切除术。采用三种不同方法阻断和/或清除肝巨噬细胞（库普弗细胞）。
我们发现，ICAM-1基因敲除型小鼠的肝脏在部分肝切除术后再生受损。这一发现与白细胞募集以及组织TNF-α和IL-6水平的显著降低有关。通过注射重组IL-6，ICAM-/-小鼠肝细胞增殖的所有指标均得以恢复。中性粒细胞减少的动物和肝巨噬细胞（库普弗细胞）清除导致类似的再生失败，TNF-α和IL-6水平较低。
数据提示了一条新途径，肝切除术后ICAM-1与白细胞结合，通过库普弗细胞依赖的TNF-α和IL-6释放触发肝细胞增殖。
