Atmani F, Mizon J, Khan S R
Univ. Florida College of Medicine, Dept. Pathology and Laboratory Medicine, Gainesville 32610-0275, USA.
Scanning Microsc. 1996;10(2):425-33; discussion 433-4.
Inter-alpha-inhibitor (I alpha I) is a serine protease inhibitor present in human plasma. It has a molecular weight of about 220 kDa which encompasses 3 chains including two heavy chains and one light chain. The light chain, known as bikunin, is responsible for the antitryptic activity of I alpha I in the inhibition of various enzymes, such as trypsin and chymotrypsin. Under physiologic or certain pathologic circumstances, several macromolecules related to I alpha I appear in plasma and urine. However, the physiologic role of I alpha I remains unclear. As far as urolithiasis is concerned, two urinary macromolecules related to I alpha I have been isolated and shown to be potent inhibitors of calcium oxalate formation. One of these inhibitors, uronic-acid-rich protein (UAP), has been identified and well characterized. The sequence of the first 18 amino acid residues of UAP is identical with that of bikunin. Furthermore, the immunoreaction between UAP and I alpha I antibody using immunoblot analysis was positive. UAP isolated from the urine of stone formers exhibited less inhibitory activity towards calcium oxalate crystallization than that derived from the urine of healthy subjects. This suggests a structural abnormality of the inhibitor obtained from stone patients. The organic matrix extracted from kidney stones contained a protein antigenically related to I alpha I. We conclude that UAP is a member of I alpha I family taking part in inhibiting calcium oxalate crystallization, and modulating the formation of stones in the urinary tract.
α-间抑制因子（IαI）是一种存在于人体血浆中的丝氨酸蛋白酶抑制剂。其分子量约为220 kDa，由3条链组成，包括两条重链和一条轻链。轻链称为比基尼，负责IαI在抑制各种酶（如胰蛋白酶和糜蛋白酶）中的抗胰蛋白酶活性。在生理或某些病理情况下，几种与IαI相关的大分子出现在血浆和尿液中。然而，IαI的生理作用仍不清楚。就尿石症而言，已分离出两种与IαI相关的尿大分子，并证明它们是草酸钙形成的有效抑制剂。其中一种抑制剂，富含糖醛酸的蛋白质（UAP），已被鉴定并得到充分表征。UAP的前18个氨基酸残基序列与比基尼的相同。此外，使用免疫印迹分析，UAP与IαI抗体之间的免疫反应呈阳性。从结石形成者尿液中分离出的UAP对草酸钙结晶的抑制活性低于从健康受试者尿液中获得的UAP。这表明从结石患者获得的抑制剂存在结构异常。从肾结石中提取的有机基质含有一种与IαI抗原相关的蛋白质。我们得出结论，UAP是IαI家族的一员，参与抑制草酸钙结晶，并调节尿路结石的形成。
