Expression of a hybrid complement regulatory protein, membrane cofactor protein decay accelerating factor on Chinese hamster ovary. Comparison of its regulatory effect with those of decay accelerating factor and membrane cofactor protein.

Expression of a hybrid complement regulatory protein, membrane cofactor protein decay accelerating factor on Chinese hamster ovary. Comparison of its regulatory effect with those of decay accelerating factor and membrane cofactor protein.
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混合补体调节蛋白、膜辅因子蛋白衰变加速因子在中国仓鼠卵巢上的表达。

DOI:
10.4049/jimmunol.152.7.3436
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发表时间:
1994
影响因子:
4.4
通讯作者:
S. Nagasawa
S. Nagasawa
中科院分区:
医学2区
文献类型:
--
作者:
K. Iwata;T. Seya;H. Ariga;S. Nagasawa

文献摘要

被引文献

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据推测,细胞表面的C活化受膜辅因子蛋白(MCP)和衰变加速因子(DAF)的调节。它们在功能上是互补的:MCP在因子I介导的C3 b和C4 b失活中充当辅因子,从而阻止C3转化酶的组装,而MCP加速组装的C3转化酶的自发衰变。本研究通过转染cDNA在中国仓鼠卵巢细胞上表达MCP-β 1,并将其调节活性与MCP和β 2转染子以及同时表达MCP和β 2的转染子(MCP + β 2)进行比较。通过激活经典途径在致敏CHO细胞上的C3沉积被这些转染子在不同程度上阻断,顺序为MCP + MCP> MCP-1> MCP-1> MCP。同样地,通过旁路途径的C3沉积被有效地阻断,顺序为杂交> MCP + MCP> MCP。C介导的CHO细胞的细胞溶解实际上反映了C3片段沉积的程度。MCP-MCP转染子获得了针对旁路途径介导的C3沉积和细胞溶解的附加保护活性,但在规避经典途径攻击方面不如单独表达MCP或MCP + MCP的细胞有效。杂合MCP-1可用于减轻C介导的细胞损伤,特别是通过旁路途径。
C activation on the cell surface is supposedly regulated by membrane cofactor protein (MCP) and decay accelerating factor (DAF). These are complementary in function: MCP acts as a cofactor in factor I-mediated C3b and C4b inactivation, thus preventing the assembly of C3 convertases, whereas DAF accelerates spontaneous decay of the assembled C3 convertase. In this report, a hybrid MCP-DAF was expressed on Chinese hamster ovary cells by transfecting cDNA, and its regulatory activity was compared with those of MCP and DAF transfectants and with a transfectant expressing both MCP and DAF (MCP + DAF). The C3 deposition on sensitized CHO cells through activation of the classical pathway was blocked to a different degree with these transfectants, the order being MCP + DAF > DAF > hybrid MCP-DAF > MCP. Likewise, the C3 deposition via the alternative pathway was blocked efficiently in the order hybrid > MCP + DAF > MCP. The C-mediated cytolysis of CHO cells virtually reflected the degree of C3 fragment deposition. The MCP-DAF transfectant acquired additive protective activity against alternative pathway-mediated C3 deposition and cytolysis but was less potent in circumventing classical pathway attack than cells that expressed DAF alone or DAF + MCP. Hybrid MCP-DAF may be useful for alleviating C-mediated cell damage, especially via the alternative pathway.