Skubitz K M, Butterfield J, Ma K, Skubitz A P
Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
Inflammation. 1998 Dec;22(6):559-72. doi: 10.1023/a:1022358313030.
The initiation of hemodialysis using cuprophane membranes is followed by a rapid fall in the circulating neutrophil count. This neutropenia is caused by a transient sequestration of neutrophils in the lung due to homotypic aggregation, largely in response to generation of C5a by contact of plasma with the dialyzer. The transient nature of hemodialysis neutropenia is due to desensitization of neutrophils to stimulation by C5a, thus demonstrating desensitization in vivo. To examine the in vivo effects on surface phenotype of continuous exposure of neutrophils to C5a over 3 h, the surface expression of 22 antigens was examined by flow cytometry in patients undergoing dialysis. Neutropenia was prominent at 15 min and absent at 60 and 180 min of dialysis. CD10, CD11b, CD11c, CD13, CD18, CD35, CD45, CD66acde, and CD66b were upregulated at 15 min and remained upregulated at 180 min. CD61 and CD63 increased slightly at 15 min and returned to baseline by 180 min. CD16 and CD62L were down regulated at 15 min and normalized by 180 min. CD15s, CDw17, CD32, and CD44 were slightly down regulated at 15 min and then returned to baseline by 180 min. CD11a, CD15, CD24, CD31, and CDw65 did not change during dialysis. This study demonstrates the changes in surface phenotype of neutrophils during prolonged in vivo exposure to C5a over 3 h, during which time neutrophils become desensitized to subsequent stimulation by similar concentrations of C5a but maintain responsiveness to other chemotactic stimuli.
使用铜仿膜开始血液透析后，循环中的中性粒细胞计数会迅速下降。这种中性粒细胞减少是由于同源聚集导致中性粒细胞短暂滞留于肺内，这主要是对血浆与透析器接触产生C5a的反应。血液透析性中性粒细胞减少的短暂性是由于中性粒细胞对C5a刺激产生脱敏，从而证明了体内脱敏现象。为了研究中性粒细胞在3小时内持续暴露于C5a对其表面表型的体内影响，通过流式细胞术检测了透析患者22种抗原的表面表达。中性粒细胞减少在透析15分钟时明显，在60分钟和180分钟时消失。CD10、CD11b、CD11c、CD13、CD18、CD35、CD45、CD66acde和CD66b在15分钟时上调，并在180分钟时仍保持上调。CD61和CD63在15分钟时略有增加，到180分钟时恢复到基线水平。CD16和CD62L在15分钟时下调，到180分钟时恢复正常。CD15s、CDw17、CD32和CD44在15分钟时略有下调，然后在180分钟时恢复到基线水平。CD11a、CD15、CD24、CD31和CDw65在透析过程中没有变化。本研究证明了中性粒细胞在体内长时间暴露于C5a超过3小时期间表面表型的变化，在此期间中性粒细胞对随后类似浓度C5a的刺激产生脱敏，但对其他趋化刺激仍保持反应性。
