Doi F, Goya T, Torisu M
First Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan.
Hepatology. 1993 Jun;17(6):1086-94.
We investigated the pathogenesis of septic liver injury in rats caused by cecal ligation and puncture. In this model, numerous neutrophils accumulated in the liver in parallel with the development of liver dysfunction. The supernatants of hepatic macrophages isolated from these septic rats 24 hr after cecal ligation and puncture had enhanced chemotactic activities for human neutrophils. These results suggest that in sepsis, hepatic macrophages attract neutrophils to the liver. Human neutrophils preincubated in this macrophage supernatant had the following biological activities not seen in the sham-operated controls. (a) They became more adherent to cultured endothelial cells through up-regulation of adhesion molecules such as CD11b/CD18, (b) their chemiluminescence was markedly elevated. These functional changes of cecal ligation and puncture hepatic macrophages were the same as those in endotoxin-pretreated hepatic macrophages after isolation from normal rats. Therefore we suspect that hepatic macrophages are activated by portal vein endotoxin in sepsis. These activated hepatic macrophages secreted chemical mediators of inflammation, including leukotriene B4 and tumor necrosis factor. In conclusion, hepatic macrophages seem to interact closely with neutrophils and play an important role in the pathogenesis of septic liver injury.
我们研究了盲肠结扎穿孔所致大鼠脓毒症性肝损伤的发病机制。在该模型中，随着肝功能障碍的发展，大量中性粒细胞在肝脏中积聚。在盲肠结扎穿孔24小时后从这些脓毒症大鼠分离的肝巨噬细胞上清液，对人中性粒细胞具有增强的趋化活性。这些结果表明，在脓毒症中，肝巨噬细胞将中性粒细胞吸引至肝脏。在此巨噬细胞上清液中预孵育的人中性粒细胞具有以下在假手术对照组中未见的生物学活性。(a) 通过上调诸如CD11b/CD18等黏附分子，它们对培养的内皮细胞的黏附性增强，(b) 其化学发光显著升高。盲肠结扎穿孔肝巨噬细胞的这些功能变化与从正常大鼠分离的内毒素预处理肝巨噬细胞的功能变化相同。因此我们推测在脓毒症中肝巨噬细胞被门静脉内毒素激活。这些活化的肝巨噬细胞分泌包括白三烯B4和肿瘤坏死因子在内的炎症化学介质。总之，肝巨噬细胞似乎与中性粒细胞密切相互作用，并在脓毒症性肝损伤的发病机制中起重要作用。
