The chondroitin sulfate chain of bikunin-containing proteins in the inter-alpha-inhibitor family increases in size in inflammatory diseases.

Inter-alpha-inhibitor (IalphaI) and pre-alpha-inhibitor (PalphaI) are the main members of a set of multichain serine proteinase inhibitors. Present in human plasma, they may be involved in control of the inflammatory process. They are composed of homologous heavy chains (H1 and H2 for IalphaI; H3 for PalphaI) covalently linked by a protein-glycosaminoglycan-protein cross-link to bikunin, which is a chondroitin 4-sulfate proteoglycan. During the acute-phase response, biosynthesis of IalphaI and PalphaI is downregulated and upregulated, respectively. In this work, we provide evidence that, in inflammatory diseases, the chondroitin sulfate chain of bikunin increases in size proportionally to the severity of the inflammatory response. As a consequence, all IalphaI-related components that contain bikunin are structurally modified. Therefore, the changes in glycosylation of the acute-phase proteins are not restricted to N-linked glycans but also affect glycosaminoglycans. The implications of these findings are discussed with regard to biosynthesis and biological role, especially the anti-inflammatory effects of IalphaI-related proteinase inhibitors.