Heavy chain transfer by tumor-necrosis-factor-stimulated-gene-6 to the bikunin proteoglycan [Glycobiology and Extracellular Matrices]

January 5th, 2015 by Lamkin, E., Cheng, G., Calabro, A., Hascall, V. C., Ji Joo, E., Li, L., Linhardt, R. J., Lauer, M. E.

We present data that hyaluronan (HA) polysaccharides, about 14-86 monosaccharides in length, were capable of accepting only a single heavy chain (HC) from inter-alpha-inhibitor via transfer by tumor-necrosis-factor-stimulated-gene-6 (TSG-6), and that this transfer was irreversible. We proposed that either the sulfate groups (or sulfation pattern) at the reducing end of bikunins chondroitin sulfate (CS) chain, or the core protein itself, enabled the bikunin proteoglycan (PG) to accept more than a single HC and permitted TSG-6 to transfer these HCs from its relatively small CS chain to HA. To test these hypotheses, we investigated HC transfer to the intact CS chain of the bikunin PG, and to bikunins free CS chain. We observed that both the free CS chain, and the intact bikunin PG, were only able to accept a single HC from ΙαΙ via transfer by TSG-6, and that HCs could be swapped from the bikunin PG, and its free CS chain, to HA. Furthermore, a significant portion of the bikunin PG was unable to accept a single heavy chain. We discuss explanations for these observations, including the intracellular assembly of inter-alpha-inhibitor. In summary, these data demonstrate that the sulfation of bikunins CS chain, and/or its core protein, promotes HC transfer by TSG-6 to its relatively short CS chain, although they are insufficient to enable bikunins CS chain to accept more than one HC in the absence of other co-factors.