Inagi R, Miyata T, Oda O, Maeda K, Inoue K
Department of Bacteriology, Osaka University Medical School, Japan.
Nephron. 1994;66(3):285-90. doi: 10.1159/000187824.
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 microM) of the activity of factor D on factor B.
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会蓄积。通过研究过量因子D对一些常见丝氨酸蛋白酶的10种合成肽底物的活性，来考察这种活性蛋白酶在这些患者中的病理生理作用。这些底物中对因子D最敏感的是Boc-Gln-Ala-Arg-MCA，它用作胰蛋白酶的底物。因子D对该底物的蛋白水解活性（2.17单位/毫克/小时）估计仅为胰蛋白酶（2.18×10⁵单位/毫克/小时）的10⁻⁵倍。因子D对其他合成底物的活性较低。因此，即使因子D在体内高度蓄积，其蛋白水解活性仍被认为对其天然底物——与C3b结合的补体因子B具有高度特异性。还研究了一些临床使用的丝氨酸蛋白酶抑制剂（甲磺酸萘莫司他、甲磺酸司匹他汀、甲磺酸卡莫司他和甲磺酸加贝酯）对因子D在其天然底物因子B上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（半数抑制浓度：25微摩尔）。
