The role of chemokines in neutrophils migration toward liver tissue in obstructive jaundice.

临床研究报告了阻塞性黄疸（OJ）患者在治疗程序（特别是大肝切除术）后并发症（如肝功能衰竭和败血症）的高发生率。外周中性粒细胞迁移在肝组织中的积累可能在这种组织损伤中起核心作用。方法：采用胆管结扎法建立OJ大鼠模型，观察中性粒细胞向胆汁淤积性肝组织迁移的机制。采用改良的Boyden小室对大鼠外周血中性粒细胞进行趋化性分析。从正常大鼠外周血中分离的中性粒细胞对OJ肝提取物具有趋化性迁移，而对正常肝提取物没有迁移。OJ大鼠中性粒细胞对OJ肝提取物有趋化反应，而对正常肝提取物无迁移反应. OJ肝提取物在肝素结合和肝素非结合组分中都含有多种中性粒细胞的化学引诱剂.与正常大鼠嗜中性粒细胞相比，OJ大鼠中性粒细胞更容易向趋化因子CINC/Gro迁移。OJ大鼠中性粒细胞对OJ大鼠肝提取液的趋化作用可被抗CINC/Gro抗体部分抑制。

Clinical studies have reported a high incidence of complications such as hepatic failure and sepsis following therapeutic procedures, particularly major hepatectomy, in patients with obstructive jaundice (OJ). Accumulation of peripheral neutrophils migration in liver tissue may play a central role in this tissue impairment. We explored the mechanism of neutrophils migration toward cholestatic liver tissue using rat animal model.Methods : OJ rat model was made with bile duct ligation. Chemotaxis assay of neutrophils separated from rat peripheral blood was performed using modified Boyden chamber.Results :1. Neutrophils separated from normal rat peripheral blood showed chemotactic migration toward OJ liver extract, while showed no migrations toward normal liver extract. The OJ rat neutrophils showed chemotactic response to OJ liver extract, while they did not show migratory response to normal liver extract.2. OJ liver extract contains multiple chemoattractants for neutrophils in both heparin-binding and heparin-nonbinding fraction.3. OJ rat neutrophils much likely to migrate toward chemokine, CINC/Gro, compared with normal rat neutrophils.4. Chemotaxis of OJ rat neutrophils to OJ rat liver extract was partially inhibited by anti-CINC/Gro antibody.In conclusion, obstructive jaundice induce increase of peripheral neutrophils motility concomitant with production of chemoattractants including chemokines in jaundiced liver tissue.