EVALUATION OF THE PROTEOLYTIC ACTIVITY OF FACTOR-D ACCUMULATED AS AN ACTIVE SERINE-PROTEASE IN PATIENTS WITH CHRONIC-RENAL-FAILURE
EVALUATION OF THE PROTEOLYTIC ACTIVITY OF FACTOR-D ACCUMULATED AS AN ACTIVE SERINE-PROTEASE IN PATIENTS WITH CHRONIC-RENAL-FAILURE
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DOI：
10.1159/000187824
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发表时间：
1994-03-01
期刊：
影响因子：
2.5
通讯作者：
INOUE, K
中科院分区：
文献类型：
--
作者：
INAGI, R;MIYATA, T;INOUE, K
补体因子D是一种补体系统丝氨酸蛋白酶，以其活性形式在体内循环，在慢性肾衰竭患者中蓄积。这种活性蛋白酶在这些患者中的病理生理作用进行了研究，过量的D因子对10合成肽底物的一些常见的丝氨酸蛋白酶的活动。这些底物中对因子D最敏感的是Boc-Gln-Ala-Arg-MCA，其用作胰蛋白酶的底物。D因子对该底物的蛋白水解活性（2.17单位/mg/h）估计是胰蛋白酶（2.18 × 10（5）单位/mg/h）的10（-5）倍。其他合成底物上D因子活性较低。因此，因子D的蛋白水解活性被认为对其天然底物，即与C3 B结合的补体因子B是非常特异的，即使当它在体内高度积累时也是如此。还研究了临床上使用的一些丝氨酸蛋白酶抑制剂（甲磺酸萘莫司他、甲磺酸塞匹司他、甲磺酸卡莫司他和甲磺酸加贝酯）对因子D对其天然底物因子B的蛋白水解活性的抑制作用。在这些合成化合物中，甲磺酸萘莫司他是因子D对因子B活性的最有效抑制剂（ID 50：25 μ M）。
Complement factor D, a complement system serine protease, circulating in vivo as its active form, accumulates in patients with chronic renal failure. The pathophysiological role of this active protease in these patients was examined by studies on activities of excess factor D on 10 synthetic peptide substrates for some usual serine proteases. The most sensitive of these substrates to factor D was Boc-Gln-Ala-Arg-MCA, which is used as a substrate for trypsin. The proteolytic activity of factor D (2.17 unit/mg/h) on this substrate was estimated to be 10(-5)-fold that of trypsin (2.18 x 10(5) unit/mg/h). The activities of factor D on other synthetic substrates were lower. Thus the proteolytic activity of factor D is considered to be very specific for its natural substrate, complement factor B bound with C3b, even when it is highly accumulated in vivo. The inhibitory effects of some serine protease inhibitors used clinically (nafamostat mesilate, sepinostat mesilate, camostat mesilate and gabexate mesilate) on the proteolytic activity of factor D on its natural substrate, factor B, were also investigated. Of these synthetic compounds, nafamostat mesilate was the most effective inhibitor (ID50:25 mu M) of the activity of factor D on factor B.