Arnaout M A, Hakim R M, Todd R F, Dana N, Colten H R
N Engl J Med. 1985 Feb 21;312(8):457-62. doi: 10.1056/NEJM198502213120801.
To identify the mechanisms accounting for hemodialysis-induced granulocytopenia, we undertook quantitative kinetic studies of a granulocyte-adhesion-promoting surface glycoprotein (Mo1). In eight patients undergoing maintenance hemodialysis, there was a fivefold increase in the mean cell-surface expression of Mo1 within 15 minutes after the start of dialysis with a new cuprophane membrane. The peak increase in surface Mo1 coincided with the maximal drop in neutrophil count and with the peak rise in the plasma levels of the complement-activation products C5a desArg and C3a desArg. During dialysis on a membrane being reused for the fifth time, no significant complement activation, no increase in Mo1 expression, and no change in neutrophil count were seen. C5a desArg (but not C3a desArg) induced a comparable increase in Mo1 expression on normal granulocytes in vitro at concentrations similar to those measured in vivo. Chemotactic peptide-induced granulocyte aggregation (a reflection of increased cell-to-cell adhesiveness) was specifically blocked by mouse monoclonal antibodies to Mo1 in vitro. These data suggest that the increased expression of Mo1 on granulocytes in vivo is in part mediated by C5a (and C5a desArg). The quantitative increase in granulocyte-surface Mo1 may provide a mechanism for initiating leukoaggregation, sequestration of granulocytes, and neutropenia during hemodialysis.
为了确定血液透析引起粒细胞减少的机制，我们对一种促进粒细胞黏附的表面糖蛋白（Mo1）进行了定量动力学研究。在8例接受维持性血液透析的患者中，使用新的铜仿膜开始透析后15分钟内，Mo1的平均细胞表面表达增加了5倍。表面Mo1的峰值增加与中性粒细胞计数的最大下降以及补体激活产物C5a desArg和C3a desArg血浆水平的峰值升高同时出现。在使用第5次的复用膜透析过程中，未观察到明显的补体激活、Mo1表达增加和中性粒细胞计数变化。C5a desArg（而非C3a desArg）在体外以与体内测量浓度相似的浓度诱导正常粒细胞上的Mo1表达出现类似增加。趋化肽诱导的粒细胞聚集（细胞间黏附增加的反映）在体外被抗Mo1小鼠单克隆抗体特异性阻断。这些数据表明，体内粒细胞上Mo1表达的增加部分由C5a（和C5a desArg）介导。粒细胞表面Mo1的定量增加可能为血液透析期间启动白细胞聚集、粒细胞隔离和中性粒细胞减少提供一种机制。
