Böhler J, Donauer J, Birmelin M, Schollmeyer P J, Hörl W H
Department of Nephrology, University of Freiburg, Germany.
Nephrol Dial Transplant. 1993;8(12):1359-65.
Granulocyte activation during haemodialysis using cuprophane membrane is mediated by complement-derived anaphylatoxins C3a and C5a. However, neutrophil degranulation induced by modified cellulosic membranes or synthetic membranes does not correlate with C3a or C5a concentrations. Incubation and recirculation experiments were performed to find out which messengers trigger neutrophil degranulation during blood contact with different membrane materials. During in vitro haemodialysis for 2 hours, PMMA and cuprophane induced pronounced degranulation of neutrophils. With PMMA this was associated with increased thromboxane B2 but low C3a levels, while with cuprophane membrane, marked complement activation but only little thromboxane B2 release was observed. Indomethacin (10 microM) nullified all thromboxane B2 response but could not influence elastase release, indicating that cyclo-oxygenase products are not involved in neutrophil degranulation under these conditions. During incubation of blood with dialysis membranes, inhibition of lipoxygenase by esculetin or of phospholipase A2 by hydrocortisone also had no effect on neutrophil degranulation. One messenger involved in granulocyte activation might be free cytosolic calcium. Application of different calcium channel blockers (verapamil, diltiazem, or nitrendipine) did not influence neutrophil degranulation in incubation experiments, in PMMA or cuprophane membranes. In contrast, chelation of plasmatic calcium by sodium citrate or EDTA blunted elastase release induced by these membranes. This study indicates that calcium is a key mediator required for neutrophil degranulation in complement-activating and non-complement-activating dialysis membranes, while activation of the prostaglandin or leukotriene cascade are not required.
使用铜仿膜进行血液透析期间的粒细胞活化是由补体衍生的过敏毒素C3a和C5a介导的。然而，由改性纤维素膜或合成膜诱导的中性粒细胞脱颗粒与C3a或C5a浓度无关。进行孵育和再循环实验以找出在血液与不同膜材料接触期间触发中性粒细胞脱颗粒的信使物质。在体外血液透析2小时期间，聚甲基丙烯酸甲酯（PMMA）和铜仿膜诱导了明显的中性粒细胞脱颗粒。对于PMMA，这与血栓素B2增加但C3a水平低有关，而对于铜仿膜，观察到明显的补体激活但仅少量血栓素B2释放。吲哚美辛（10微摩尔）消除了所有血栓素B2反应，但不能影响弹性蛋白酶释放，表明在这些条件下环氧化酶产物不参与中性粒细胞脱颗粒。在血液与透析膜孵育期间，七叶亭抑制脂氧合酶或氢化可的松抑制磷脂酶A2对中性粒细胞脱颗粒也没有影响。参与粒细胞活化的一种信使物质可能是游离的胞质钙。在孵育实验中，在PMMA或铜仿膜中应用不同的钙通道阻滞剂（维拉帕米、地尔硫卓或尼群地平）不影响中性粒细胞脱颗粒。相反，柠檬酸钠或乙二胺四乙酸（EDTA）螯合血浆钙会减弱这些膜诱导的弹性蛋白酶释放。这项研究表明，钙是补体激活和非补体激活透析膜中中性粒细胞脱颗粒所需的关键介质，而前列腺素或白三烯级联的激活则不是必需的。
