title: Transfer of inter-alpha-inhibitor heavy chains to hyaluronan by surface-linked hyaluronan-TSG-6 complexes.
abstract: 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.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Colón
authors.forename: Anastasia
authors.initials: A
authors.lastname: Shytuhina
authors.forename: Mary K
authors.initials: MK
authors.lastname: Cowman
authors.forename: Philip A
authors.initials: PA
authors.lastname: Band
authors.forename: Kristian W
authors.initials: KW
authors.lastname: Sanggaard
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Enghild
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Wisniewski
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D008670:Metals / Q000378:metabolism; D009994:Osmolar Concentration; D011485:Protein Binding
chemical_list: D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D008670:Metals; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid