Hisama N, Yamaguchi Y, Ishiko T, Miyanari N, Ichiguchi O, Goto M, Mori K, Watanabe K, Kawamura K, Tsurufuji S, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Japan.
Hepatology. 1996 Nov;24(5):1193-8. doi: 10.1053/jhep.1996.v24.pm0008903397.
We investigated the role of hepatic macrophages in the inflammatory response following reperfusion injury by blocking Kupffer cell phagocytosis with gadolinium chloride (GdCl3). Liver ischemia was induced in rats by occluding the portal vein for 30 minutes. A bolus of GdCl3 (7 mg/kg) was injected intravenously 1 and 2 days before surgery. The serum levels of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, peaked after 6 hours, and then gradually decreased. GdCl3 or heparin alone significantly decreased the serum levels of CINC (P < .05). In addition, pretreatment with GdCl3/heparin further inhibited the rise in the serum levels of CINC following reperfusion compared with those in untreated animals (P < .01). The in vitro production of CINC by Kupffer cells, obtained from animals pretreated with heparin or GdCl3, was significantly lower than that of cells isolated from untreated animals. Pretreatment with GdCl3/heparin further decreased CINC production by Kupffer cells compared with that of cells from animals that were pretreated with heparin or GdCl3 alone. The expression of CINC transcripts in Kupffer cells or in liver tissue peaked 3 hours after reperfusion in untreated animals. Pretreatment with heparin, GdCl3, or both significantly decreased the levels of CINC messenger RNA (mRNA) transcripts. Pretreatment with heparin, GdCl3, or GdCl3/heparin significantly decreased the number of neutrophils that accumulated in the liver 24 hours following reperfusion, compared with those in untreated animals. These results suggest that Kupffer cells release CINC and may play an important role in early neutrophil infiltration into the liver following ischemia/reperfusion.
我们通过用氯化钆（GdCl3）阻断枯否细胞吞噬作用，研究了肝巨噬细胞在再灌注损伤后炎症反应中的作用。通过阻断门静脉30分钟诱导大鼠肝脏缺血。在手术前1天和2天静脉注射一剂GdCl3（7mg/kg）。未治疗大鼠再灌注后血清细胞因子诱导的中性粒细胞趋化因子（CINC）水平升高，6小时后达到峰值，然后逐渐下降。单独使用GdCl3或肝素可显著降低CINC的血清水平（P<.05）。此外，与未治疗动物相比，用GdCl3/肝素预处理进一步抑制了再灌注后CINC血清水平的升高（P<.01）。从用肝素或GdCl3预处理的动物获得的枯否细胞体外产生的CINC显著低于从未治疗动物分离的细胞。与单独用肝素或GdCl3预处理的动物的细胞相比，用GdCl3/肝素预处理进一步降低了枯否细胞产生的CINC。未治疗动物再灌注后3小时，枯否细胞或肝组织中CINC转录物的表达达到峰值。用肝素、GdCl3或两者预处理显著降低了CINC信使核糖核酸（mRNA）转录物的水平。与未治疗动物相比，用肝素、GdCl3或GdCl3/肝素预处理显著减少了再灌注后24小时肝脏中积聚的中性粒细胞数量。这些结果表明，枯否细胞释放CINC，可能在缺血/再灌注后早期中性粒细胞浸润肝脏中起重要作用。
