Deaciuc I V, Bagby G J, Niesman M R, Skrepnik N, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393.
Hepatology. 1994 Feb;19(2):464-70.
We tested the hypothesis that Kupffer cells modulate sinusoidal endothelial cell function in the liver. Rats were treated with Kupffer cell-depleting agents (gadolinium chloride and liposome-encapsulated dichloromethylene diphosphonate) or with inhibitors of phospholipase A2 or leukotriene A4 synthase (dexamethasone and diethylcarbamazine, respectively). Hyaluronan uptake by the isolated, perfused liver was measured as an index of the functional state of the sinusoidal endothelial cell. Plasma hyaluronan concentration was also determined. Three hours after Escherichia coli lipopolysaccharide administration (100 micrograms/100 gm body wt, intravenously) plasma hyaluronan levels were significantly increased (280% to 320%), whereas hepatic hyaluronan uptake was markedly decreased (approximately 76%). Pretreatment with gadolinium chloride (0.5 mg/100 gm body wt, intravenously, 21 hr before saline solution or lipopolysaccharide administration), liposome-encapsulated dichloromethylene diphosphonate (40 mumol/100 gm body wt, intravenously, 44 hr before saline solution or lipopolysaccharide injection), dexamethasone (40 micrograms/100 gm body wt, intravenously, 1 hr before saline solution or lipopolysaccharide administration) or diethylcarbamazine (repeated doses, 10 mg/100 gm body wt, intravenously, 1 hr before saline solution or lipopolysaccharide injection) counteracted the lipopolysaccharide inhibitory effect on hepatic hyaluronan uptake. With the exception of gadolinium chloride, all other agents also prevented the lipopolysaccharide-induced increase in plasma hyaluronan concentration. Gadolinium chloride only attenuated the lipopolysaccharide effect on plasma hyaluronan level. Taken together with earlier results from our laboratory, these data indicate that: (a) Kupffer cell activation by lipopolysaccharide results in suppression of hyaluronan uptake by sinusoidal endothelial cells and (b) such modulation of endothelial cell function is likely mediated by products of the lipoxygenase pathway of arachidonate metabolism.
库普弗细胞可调节肝脏中肝血窦内皮细胞的功能。用清除库普弗细胞的药物（氯化钆和脂质体包裹的二氯亚甲基二膦酸盐）或磷脂酶A2或白三烯A4合酶抑制剂（分别为地塞米松和乙胺嗪）处理大鼠。测量分离灌注肝脏对透明质酸的摄取，以此作为肝血窦内皮细胞功能状态的指标。同时也测定血浆透明质酸浓度。静脉注射大肠杆菌脂多糖（100微克/100克体重）3小时后，血浆透明质酸水平显著升高（280%至320%），而肝脏对透明质酸的摄取则明显降低（约76%）。在注射生理盐水或脂多糖前21小时静脉注射氯化钆（0.5毫克/100克体重）、在注射生理盐水或脂多糖前44小时静脉注射脂质体包裹的二氯亚甲基二膦酸盐（40微摩尔/100克体重）、在注射生理盐水或脂多糖前1小时静脉注射地塞米松（40微克/100克体重）或乙胺嗪（重复给药，10毫克/100克体重，在注射生理盐水或脂多糖前1小时静脉注射），均可抵消脂多糖对肝脏摄取透明质酸的抑制作用。除氯化钆外，所有其他药物还可防止脂多糖诱导的血浆透明质酸浓度升高。氯化钆仅减弱脂多糖对血浆透明质酸水平的影响。结合我们实验室早期的研究结果，这些数据表明：（a）脂多糖激活库普弗细胞会导致肝血窦内皮细胞对透明质酸的摄取受到抑制；（b）内皮细胞功能的这种调节可能是由花生四烯酸代谢的脂氧合酶途径的产物介导的。
