Himmelfarb J, Holbrook D, McMonagle E
Division of Nephrology, Maine Medical Center, Portland 04102.
Am J Kidney Dis. 1994 Dec;24(6):901-6. doi: 10.1016/s0272-6386(12)81058-4.
Hemodialysis with cellulosic membranes results in complement activation, granulocytopenia, and granulocyte activation. To further investigate the relationship between complement activation and granulocyte activation, we developed a model of ex vivo hemodialysis with blood flow, dialysate flow, and dialysate composition similar to in vivo hemodialysis. We used this model to investigate the effects of aprotinin, a potent serine protease inhibitor frequently used as an anti-inflammatory agent during cardiopulmonary bypass surgery, on both complement and granulocyte activation. Seven normal human volunteers were phlebotomized for ex vivo hemodialysis on two occasions each, one with and once without 800,000 kallikrein inhibitor units of aprotinin added to the circuit. Measurements were made of complement activation (radioimmunoassay for C3a desArg and C5a desArg), as well as granulocyte activation (flow cytometric measurements of reactive oxygen species (ROS) production, granulocyte CD11b-CD18 [MAC-1, CR3] expression, and CD62-L [L-selectin] expression). Statistically significant elevations in C3a desArg levels occurred by 10 minutes and reached a maximum of 5,367 +/- 712 ng/mL by 60 minutes after the initiation of ex vivo hemodialysis. Plasma C5a levels were elevated to 236 +/- 32 ng/mL at 60 minutes compared with 45 +/- 15 ng/mL predialysis. Aprotinin was able to significantly inhibit dialysis-induced C3a generation (peak 2,456 +/- 572 ng/mL at 60 minutes) as well as C5a generation (86 +/- 23 ng/mL at 60 minutes). During ex vivo hemodialysis, there was also a significant increase in granulocyte ROS production, MAC-1 upregulation, and L-selectin downregulation. Changes in granulocyte activation were not affected by the administration of aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)
使用纤维素膜进行血液透析会导致补体激活、粒细胞减少和粒细胞活化。为了进一步研究补体激活与粒细胞活化之间的关系，我们建立了一个体外血液透析模型，其血流、透析液流量和透析液成分与体内血液透析相似。我们使用该模型研究抑肽酶（一种在体外循环手术中常用作抗炎剂的强效丝氨酸蛋白酶抑制剂）对补体和粒细胞活化的影响。7名正常人类志愿者每人进行两次体外血液透析采血，一次在回路中添加80万激肽释放酶抑制单位的抑肽酶，另一次不添加。测量补体激活（C3a去精氨酸和C5a去精氨酸的放射免疫测定）以及粒细胞活化（活性氧（ROS）产生、粒细胞CD11b - CD18 [MAC - 1，CR3]表达和CD62 - L [L - 选择素]表达的流式细胞术测量）。体外血液透析开始后10分钟，C3a去精氨酸水平出现统计学显著升高，60分钟时达到最大值5367±712 ng/mL。60分钟时血浆C5a水平升至236±32 ng/mL，而透析前为45±15 ng/mL。抑肽酶能够显著抑制透析诱导的C3a生成（60分钟时峰值为2456±572 ng/mL）以及C5a生成（60分钟时为86±23 ng/mL）。在体外血液透析期间，粒细胞ROS产生、MAC - 1上调和L - 选择素下调也有显著增加。粒细胞活化的变化不受抑肽酶给药的影响。（摘要截断于250字）
