中性内肽酶对脓毒性休克的调节作用
Neutral endopeptidase modulation of septic shock.
作者信息
Lu B, Gerard N P, Kolakowski L F, Bozza M, Zurakowski D, Finco O, Carroll M C, Gerard C
机构信息
Ina Sue Perlmutter Laboratory, Children's Hospital, Boston, Massachusetts, USA.
出版信息
J Exp Med. 1995 Jun 1;181(6):2271-5. doi: 10.1084/jem.181.6.2271.
Abstract
Neutral endopeptidase (NEP; EC. 3.4.24.11) is a type 2 cell surface metalloprotease known by a variety of eponyms, including enkephalinase, common acute lymphoblastic leukemia antigen, and CD10. Identified substrates are largely neural or humoral oligopeptide agonists, and the enzyme functions to terminate signaling by degrading the ligand, analogously to acetylcholine/acetylcholinesterase. Targeted disruption of the NEP locus in mice results in enhanced lethality to endotoxin shock with a pronounced gene dosage effect. The site(s) of action appears downstream from release of tumor necrosis factor and interleukin-1 since NEP-deficient animals demonstrate increased sensitivity to these mediators as well. This unexpected finding indicates an important protective role for NEP in septic shock.
摘要
中性内肽酶（NEP；EC. 3.4.24.11）是一种2型细胞表面金属蛋白酶，有多种别名，包括脑啡肽酶、普通急性淋巴细胞白血病抗原和CD10。已确定的底物大多是神经或体液寡肽激动剂，该酶通过降解配体来终止信号传导，类似于乙酰胆碱/乙酰胆碱酯酶。在小鼠中靶向破坏NEP基因座会导致对内毒素休克的致死率增加，并具有明显的基因剂量效应。作用位点似乎在肿瘤坏死因子和白细胞介素-1释放的下游，因为NEP缺陷动物对这些介质也表现出更高的敏感性。这一意外发现表明NEP在脓毒性休克中具有重要的保护作用。
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