Goldblum S E, Van Epps D E, Reed W P
J Clin Invest. 1979 Jul;64(1):255-64. doi: 10.1172/JCI109446.
Abnormal granulocyte chemotaxis has been described in chronic hemodialysis patients. In this study, sera from 53 hemodialysis patients were tested for chemotactic inhibitory activity by a modified Boyden technique. Chemotactic inhibitory activity, defined as >20% inhibition of normal granulocyte chemotaxis, was found in 45% of patients. Only sera from patients having undergone >3 mo hemodialysis displayed chemotactic inhibitory activity and retained this inhibitory activity when retested 9 mo later. Four of five patients who had initially undergone <3 mo hemodialysis and lacked serum chemotactic inhibitory activity developed inhibitory activity when tested 9 mo later. Clinical evaluation of patients with serum chemotactic inhibitory activity showed that these patients did not have a significantly increased incidence of infection, although a trend toward decreased mortality during the time of study was observed (P = 0.0721). Serum chemotactic inhibitory activity was heat stable at 56 degrees C for 30 min and concentration dependent. The major inhibitory component was found to have a sedimentation coefficient of 4S by sucrose density gradient centrifugation. The chemotactic inhibitory activity was not precipitated by 30% ammonium sulfate, but was partially precipitated by 50% ammonium sulfate. Inhibitory sera effectively suppressed neutrophil migration in response to chemotactic C5 fragment and Escherichia coli derived chemotactic factor but was least effective in a system mediated by casein. Furthermore, normal neutrophils preincubated in hemodialysis patient sera displayed normal chemotactic responsiveness indicating a lack of cell-directed inhibition. Serum fractions that contained the inhibitor were found to directly act on the chemotactic C5 fragment, reducing its chemotactic activity. This study indicates that a circulating 4S, heat-stable, factor-directed inhibitor of granulocyte chemotaxis is present in the sera of many hemodialysis patients and probably results from the hemodialysis procedure.
慢性血液透析患者中已发现粒细胞趋化异常。在本研究中，采用改良的博伊登技术对53例血液透析患者的血清进行趋化抑制活性检测。趋化抑制活性定义为对正常粒细胞趋化的抑制率>20%，在45%的患者中发现有该活性。只有透析时间超过3个月的患者血清显示出趋化抑制活性，且在9个月后重新检测时仍保留该抑制活性。最初透析时间不足3个月且缺乏血清趋化抑制活性的5例患者中，有4例在9个月后检测时出现了抑制活性。对具有血清趋化抑制活性的患者进行临床评估发现，这些患者的感染发生率并未显著增加，尽管在研究期间观察到死亡率有下降趋势（P = 0.0721）。血清趋化抑制活性在56℃下加热30分钟后仍保持稳定，且呈浓度依赖性。通过蔗糖密度梯度离心发现，主要抑制成分的沉降系数为4S。30%硫酸铵不能使趋化抑制活性沉淀，但50%硫酸铵可使其部分沉淀。抑制性血清能有效抑制中性粒细胞对趋化C5片段和大肠杆菌来源的趋化因子的迁移反应，但在酪蛋白介导的系统中效果最差。此外，在血液透析患者血清中预孵育的正常中性粒细胞显示出正常的趋化反应性，表明不存在细胞定向抑制。发现含有抑制剂的血清组分可直接作用于趋化C5片段，降低其趋化活性。本研究表明，许多血液透析患者的血清中存在一种循环的4S、热稳定、针对因子的粒细胞趋化抑制剂，这可能是血液透析过程导致的。
