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

Inter-alpha -inhibitor (I alphaI) and pre-alpha -inhibitor (P alphaI) are t he main members of a set of multichain serine proteinase inhibitors. Presen t in human plasma, they may be involved in control of the inflammatory proc ess. They are composed of homologous heavy chains (H1 and H2 for I alphaI; H3 for P alphaI) covalently linked by a protein-glycosaminoglycan-protein c ross-link to bikunin, which is a chondroitin 4-sulfate proteoglycan. During the acute-phase response, biosynthesis of I alphaI and P alphaI is downreg ulated and upregulated, respectively. In this work, we provide evidence that, in inflammatory diseases, the chond roitin sulfate chain of bikunin increases in size proportionally to the sev erity of the inflammatory response. As a consequence, all I alphaI-related components that contain bikunin are structurally modified. Therefore, the c hanges 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 biosynthesi s and biological role, especially the anti-inflammatory effects of I alphaI -related proteinase inhibitors.