AUTOIMMUNOREGULATION - DIFFERENTIAL MODULATION OF CD10 NEUTRAL ENDOPEPTIDASE 24.11 BY TUMOR-NECROSIS-FACTOR AND NEUROPEPTIDES
AUTOIMMUNOREGULATION - DIFFERENTIAL MODULATION OF CD10 NEUTRAL ENDOPEPTIDASE 24.11 BY TUMOR-NECROSIS-FACTOR AND NEUROPEPTIDES
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DOI：
10.1016/0165-5728(92)90189-r
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发表时间：
1992-11-01
影响因子：
3.3
通讯作者：
HUGHES, TK
中科院分区：
文献类型：
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作者：
STEFANO, GB;PAEMEN, LR;HUGHES, TK
中性内肽酶(NEP)24.11似乎是脊椎动物和无脊椎动物自身免疫调节中的一个重要酶。表达NEP的人或无脊椎动物免疫细胞用单因子和神经肽等底物激活后，NEP的表达增加，换句话说，上调。然而，由于某些神经肽也是NEP的底物，这些激活的免疫细胞只有在较高浓度时才会对神经肽产生反应，从而下调反应。具体地说，在肿瘤坏死因子(TNF)处理的免疫细胞中，我们证明了NEP表达增加对神经肽甲硫氨酸脑啡肽、黑素细胞刺激素和P物质刺激活性的影响。我们证明了NEP在调节这些反应中的意义，通过使用特定的酶抑制剂，如磷酰胺、硫胺和卡托普利。此外，我们提出的证据表明，来自不同和相同捐赠者的免疫细胞对激活物质的个体差异可能反映了内源性刺激所表达的NEP水平的波动。这些结果表明，NEP是控制人类和高等无脊椎动物某些免疫细胞对单因子和神经肽等生物活性物质影响的反应(S)的一个极显著的因素。
Neutral endopeptidase (NEP) 24.11 appears to be an important enzyme in both vertebrate and invertebrate autoimmunoregulation. Activation of human or invertebrate immunocytes that express NEP with substrates such as monokines and neuropeptides results in its increased expression, in other words, upregulation. However, since certain neuropeptides are also substrates for NEP, these activated immunocytes will respond to neuropeptides only at higher concentrations, thus downregulating the response. Specifically, in tumor necrosis factor (TNF)-treated immunocytes, we demonstrate the effects of increased NEP expression on altering the stimulatory activities of the neuropeptides met-enkephalin, melanocyte-stimulating hormone and substance P. We demonstrate the significance of NEP in modulating these responses through the use of specific enzyme inhibitors such as phosphoramidon, thiorphan and captopril. Furthermore, we present evidence suggesting that the individual variations seen in immunocytes from both different and the same donors to activating substances may reflect fluctuating levels of NEP expressed in response to endogenous stimuli. These results indicate that NEP is a highly significant factor in controlling the response(s) of certain immunocytes in man and higher invertebrates to the influence of biologically active substances such as monokines and neuropeptides.