Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation.
Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation.
复制标题
补体膜辅因子蛋白（MCP）的定量分析。
作者：
T. Seya;T. Hara;M. Matsumoto;H. Akedo
膜辅因子蛋白（MCP）是一种细胞相关的C系统调节分子，具有C3 b/C4 b结合和I因子依赖性辅因子活性。产生抗MCP的mAb，并在正常人细胞和细胞系上检查其量和分布。正常血细胞中MCP的平均含量为3000 ~ 7000拷贝/细胞，E细胞中无MCP。值得注意的是，PMN直到在37 ℃下孵育超过30分钟才完全显示所有MCP位点。在大多数肿瘤细胞系中，除了B细胞系，MCP的表达与正常细胞相比增加了2- 8倍。引人注目的是，骨髓细胞系的重组粒细胞CSF治疗和成红细胞样细胞系K562的氯化血红素治疗导致MCP降低至接近正常水平。与此相反，C3 b/C4 b受体（CR 1）往往增加与粒细胞-CSF治疗在几个细胞系。我们同时测定了这些肿瘤细胞中的衰变加速因子（decay-accelerating factor，CRF）和CR 1的水平，并通过激活替代C途径测试了对C3沉积的敏感性。在我们检测的21个细胞系中，14个缺乏CR 1，2个缺乏MCP;然而，没有一个缺乏MCP。在一些髓系细胞系和EBV感染的B细胞系中观察到少量的C3沉积。然而，C3沉积并没有反映出调节蛋白的缺陷。携带MCP的肿瘤细胞，缺乏CR 1或CR 4，并且没有经历C3沉积，可能由于在缺乏其他调节蛋白的情况下MCP的补偿作用而逃避C攻击。MCP的高表达为肿瘤细胞阻断C攻击并在血流中存活提供了便利的手段。我们倾向于这样的解释，即MCP与某些恶性疾病相关，并且细胞分化导致从MCP主导状态转换为CR 1主导状态。
Membrane cofactor protein (MCP) is a cell-associated regulatory molecule for C system with C3b/C4b binding and factor I-dependent cofactor activity. mAb were raised against MCP and amounts and distribution examined on normal human cells and cell lines. The mean quantity of MCP was 3000 to 7000 copies/cell in normal blood cells, except for E which have no MCP. Of note, PMN did not fully reveal all MCP sites until incubated for greater than 30 min at 37 degrees C. In most tumor cell lines, except for B cell lineages, expression of MCP increased by 2- to 8-fold in comparison with the normal cell counterparts. Strikingly, recombinant granulocyte CSF treatment of myeloid cell lines and hemin treatment of an erythroblastoid cell line, K562, led to a decrease of MCP to near normal levels. In contrast, C3b/C4b receptor (CR1) tended to increase with granulocyte-CSF treatment in several cell lines. We simultaneously determined levels of decay-accelerating factor (DAF) and CR1 in these tumor cells, and tested susceptibility to C3 deposition via activation of the alternative C pathway. Of 21 cell lines we examined, 14 lacked CR1 and two lacked DAF; none, however, lacked MCP. A slight amount of C3 deposition was observed in some myeloid cell lines and EBV-infected B cell lines. However, C3 deposition did not reflect a defect in the regulatory proteins. Tumor cells bearing MCP, lacking CR1 or DAF, and undergoing no C3 deposition, may escape C attack due to the compensatory effect of MCP in the absence of the other regulatory proteins. High expression of MCP provides a convenient means for tumor cells to block C attack and survive in blood stream. We favor the interpretation that MCP is up-regulated in association with certain malignant disorders, and that cell differentiation results in a switch from an MCP-dominant state to a CR1-dominant state.