Colón Elisa, Shytuhina Anastasia, Cowman Mary K, Band Philip A, Sanggaard Kristian W, Enghild Jan J, Wisniewski Hans-Georg
Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
J Biol Chem. 2009 Jan 23;284(4):2320-31. doi: 10.1074/jbc.M807183200. Epub 2008 Nov 25.
Inter-alpha-inhibitor, TSG-6, and hyaluronan have important functions in fertility and inflammation. Two subunits of inter-alpha-inhibitor, the heavy chains, form covalent bonds with TSG-6 or hyaluronan in vitro. TSG-6-heavy chain complexes serve as intermediates in the transfer of heavy chains from inter-alpha-inhibitor to hyaluronan. In vivo, in addition to these complexes, stable ternary complexes of hyaluronan with both TSG-6 and heavy chains have been demonstrated in the ovulatory cumulus oophorus. In our ongoing efforts to characterize the multiple interactions between hyaluronan, TSG-6 and inter-alpha-inhibitor, we recently characterized the formation of highly stable complexes of TSG-6 with hyaluronan that had been tethered to a solid surface. Here we show that these hyaluronan-TSG-6 complexes are functionally active and transfer heavy chain subunits from inter-alpha-inhibitor to either free or surface-bound hyaluronan. Transitional hyaluronan-TSG-6-heavy chain complexes do not accumulate in vitro. Our data show the capability for heavy chain transfer by both free TSG-6 and preformed hyaluronan-TSG-6 complexes, suggesting that both might contribute to hyaluronan modification in vivo. Transfer of heavy chains to surface-tethered hyaluronan by either free TSG-6 or surface-tethered hyaluronan-TSG-6 complexes did not affect the CD 44-mediated binding of BW 5147 cells in vitro. We show how TSG-6 and hyaluronan together can deplete inter-alpha-inhibitor and generate bikunin, as has been observed in sepsis, and discuss the role of TSG-6 in the generation of hyaluronan-heavy chain complexes associated with ovulation, arthritis, and sepsis.
α-间抑制剂、TSG-6和透明质酸在生育和炎症中具有重要作用。α-间抑制剂的两个亚基，即重链，在体外与TSG-6或透明质酸形成共价键。TSG-6-重链复合物作为重链从α-间抑制剂转移到透明质酸的中间体。在体内，除了这些复合物外，在排卵的卵丘中还证实了透明质酸与TSG-6和重链的稳定三元复合物。在我们持续努力表征透明质酸、TSG-6和α-间抑制剂之间的多种相互作用时，我们最近表征了TSG-6与固定在固体表面的透明质酸形成的高度稳定复合物的形成。在这里，我们表明这些透明质酸-TSG-6复合物具有功能活性，并将重链亚基从α-间抑制剂转移到游离或表面结合的透明质酸上。过渡性透明质酸-TSG-6-重链复合物在体外不会积累。我们的数据显示了游离TSG-6和预先形成的透明质酸-TSG-6复合物都具有重链转移能力，这表明两者都可能在体内促进透明质酸修饰。游离TSG-6或表面固定的透明质酸-TSG-6复合物将重链转移到表面固定的透明质酸上，在体外不会影响BW 5147细胞的CD 44介导的结合。我们展示了TSG-6和透明质酸如何一起消耗α-间抑制剂并产生比基尼，正如在脓毒症中所观察到的那样，并讨论了TSG-6在与排卵、关节炎和脓毒症相关的透明质酸-重链复合物形成中的作用。
