INHIBITION OF INVITRO NATURAL-KILLER ACTIVITY BY THE 3RD COMPONENT OF COMPLEMENT - ROLE FOR THE C3A FRAGMENT

INHIBITION OF INVITRO NATURAL-KILLER ACTIVITY BY THE 3RD COMPONENT OF COMPLEMENT - ROLE FOR THE C3A FRAGMENT
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DOI:
10.1073/pnas.79.19.6003
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发表时间:
1982-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
通讯作者:
FRADE, R
FRADE, R
中科院分区:
其他
文献类型:
--
作者:
CHARRIAUT, C;SENIK, A;FRADE, R

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纯化的人天然C3(补体成分3)在小鼠和人体系中均抑制体外自然杀伤(NK)细胞的细胞毒性。该作用具有剂量和时间依赖性,在NK测定期间或效应细胞与190 nM C3(35μg/ml)预孵育30分钟后,可达到50%的抑制。C3作用于效应细胞群体水平,因为对靶细胞进行预处理不会改变NK裂解。这种抑制不是由于普遍的细胞毒性,也不是由于细胞凝集。另一种体外细胞毒性系统(由同种反应性细胞毒性淋巴细胞代表)不受纯化C3的影响。对C3分子活性部分的结构分析表明,C3诱导的抑制由C3a片段支持。羧肽酶B释放羧基末端精氨酸残基,将C3a转化为去精氨酸77 - C3a,并没有改变该片段所显示的抑制作用。C3a可能在NK活性的调节中起重要作用。
Purified human native C3 [complement component 3] inhibited in vitro natural killer (NK) cell cytotoxicity in both mouse and human systems. The effect was dose and time dependent, a 50% inhibition being reached with 190 nM C3 (35 .mu.g/ml) added during the NK assay or after a 30 min preincubation of the effector cells with this C3 concentration. C3 acted at the effector-cell population level because pretreatment of the target cells did not modify the NK lysis. The inhibition was not due to general cytotoxicity nor to cell agglutination. Another in vitro cytotoxicity system (represented by alloreactive cytotoxic lymphocytes) was not affected by purified C3. Structural analysis of the active part of the C3 molecule shows that the C3-induced inhibition is supported by the C3a fragment. Release of carboxyl-terminal arginine residue by carboxypeptidase B, converting C3a into des-Arg77-C3a, did not alter the inhibitory effect displayed by this fragment. C3a may play an important role in the regulation of NK activity.