Equivalent involvement of inter-alpha-trypsin inhibitor heavy chain isoforms in forming covalent complexes with hyaluronan.

Inter-alpha-trypsin inhibitor (IalphaI) family molecules are composed of a common light chain of chondroitin sulfate proteoglycan, bikunin, and one or two of three genetically distinct heavy chain isoforms (designated HC1, 2, 3) that are bound covalently to the chondroitin sulfate chain. Hyaluronan can substitute for chondroitin sulfate to form a covalent complex with HCs. Important physiological and pathological roles of the formation of HC-hyaluronan complex have been well established. However, the involvement of the three HC isoforms in the assembly of IalphaI family molecules and the subsequent formation of SHAP-hyaluronan complex has not been studied yet in mice. In this study, we showed that mouse IalphaI and pre-alpha inhibitor contain HC1 approximately HC3 and HC3, respectively. All three HC isoforms are found in the SHAP-hyaluronan complexes of physiological or pathological origins as well as that formed in vitro, indicating that the three HC isoforms are all potential in forming complex with hyaluronan.