Inter-alpha-inhibitor: A protein family involved in the inhibition of calcium oxalate crystallization

Inter-α-inhibitor (IαI) 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 IαI in the inhibition of various enzymes, such as trypsin and chymotrypsin. Under physiologic or certain pathologic circumstances, several macromolecules related to IαI appear in plasma and urine. However, the physiologic role of IαI remains unclear. As far as urolithiasis is concerned, two urinary macromolecules related to IαI have been isolated and shown to be potent inhibitors of calcium oxalate formation. One of these inhibitors, uronic- acid-rich protein (UAP), has been identitled 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 IαI 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 antigenitally related to IαI. We conclude that UAP is a member of IαI family taking part in inhibiting calcium oxalate crystallization, and modulating the formation of stones in the urinary tract.