SOLUBLE LIPOPOLYSACCHARIDE RECEPTOR (CD14) IS RELEASED VIA 2 DIFFERENT MECHANISMS FROM HUMAN MONOCYTES AND CD14 TRANSFECTANTS

SOLUBLE LIPOPOLYSACCHARIDE RECEPTOR (CD14) IS RELEASED VIA 2 DIFFERENT MECHANISMS FROM HUMAN MONOCYTES AND CD14 TRANSFECTANTS
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DOI:
10.1002/eji.1830250244
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发表时间:
1995-02-01
影响因子:
5.4
通讯作者:
ENGELMANN, H
ENGELMANN, H
中科院分区:
医学3区
文献类型:
--
作者:
BUFLER, P;STIEGLER, G;ENGELMANN, H

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脂多糖LPS的受体(CD 14)以膜结合(mCD 14)和可溶性形式(sCD 14)存在。先前的研究表明,单核细胞通过膜结合受体的有限蛋白水解产生sCD 14。在这项研究中,我们证明,人类单核细胞也产生sCD 14的蛋白酶独立的机制。为了研究第二种途径的分子性质,我们研究了单核细胞系Mono Mac 6(MM 6)和CD 14转染子中的sCD 14形成。MM 6和CD 14转染子均通过蛋白酶非依赖性机制组成性产生sCD 14。由CD 14转染子产生的sCD 14的结构分析再次证实了从cDNA预测的COOH末端的存在。由于糖基磷脂酰肌醇锚连接与疏水性C-末端信号肽的去除,我们的研究结果表明,转染子分泌sCD 14逃脱这种翻译后修饰。从肾功能不全患者的腹膜透析液中获得的sCD 14的相同结果表明,该途径与sCD 14的产生具有体内相关性。
The receptor for lipopolysaccharide LPS (CD14) exists in a membrane-associated (mCD14) and a soluble form (sCD14). Previous studies indicate that monocytes produce sCD14 by limited proteolysis of the membrane-bound receptor. In this study we demonstrate that human monocytes also produce sCD14 by a protease-independent mechanism. To investigate the molecular nature of this second pathway we studied sCD14 formation in the monocytic cell line Mono Mac 6 (MM6) and in CD14 transfectants. Both MM6 and the CD14 transfectants constitutively produce sCD14 by a protease-independent mechanism. Structural analysis of sCD14 produced by the CD14 transfectants reconfirmed the presence of the CO OH terminus predicted from the cDNA. Since glycosylphosphatidylinositol anchor attachment is associated with the removal of a hydrophobic C-terminal signal peptide, our finding demonstrates that the transfectants secrete sCD14 which escaped this posttranslational modification. Identical results obtained for sCD14 derived from peritoneal dialysis fluid of a patient with kidney dysfunction show the in vivo relevance of this pathway for sCD14 production.