### Inter-$\alpha$-inhibitor Impairs TSG-6-induced Hyaluronan Cross-linking.

Under inflammatory conditions and in the matrix of the cumulus-oocyte complex, the polysaccharide hyaluronan (HA) becomes decorated covalently with heavy chains (HCs) of the serum glycoprotein inter-$\alpha$-inhibitor (I$\alpha$I). This alters the functional properties of the HA as well as its structural role within extracellular matrixes. The covalent transfer of HCs from I$\alpha$I to HA is catalyzed by TSG-6 (tumor necrosis factor-stimulated gene-6), but TSG-6 is also known as a HA cross-linker that induces condensation of the HA matrix. Here, the interplay of these two distinct functions of TSG-6 was investigated by studying the ternary interactions of I$\alpha$I and TSG-6 with well defined films of end-grafted HA chains. It is demonstrated that TSG-6-mediated crosslinking of HA films is impaired in the presence of I$\alpha$I and that this effect suppresses the TSG-6-mediated enhancement of HA binding to CD44-pos. cells. Furthermore, it is found that the interaction of TSG-6 and I$\alpha$I in the presence of HA gives rise to two types of complexes that independently promote the covalent transfer of heavy chains to HA. One type of complex interacts very weakly with HA and is likely to correspond to the previously reported covalent HC·TSG-6 complexes. The other type of complex is novel and binds stably but non-covalently to HA. Prolonged incubation with TSG-6 and I$\alpha$I leads to HA films that contain, in addn. to covalently HA-bound HCs, several tightly but non-covalently bound mol. species. These findings have important implications for understanding how the biol. activities of TSG-6 are regulated, such that the presence or absence of I$\alpha$I will dictate its function. [on SciFinder(R)]

### Références

Titre
Inter-$\alpha$-inhibitor Impairs TSG-6-induced Hyaluronan Cross-linking.
Type de publication
Article de revue
Année de publication
2013
Revue
J. Biol. Chem.
Volume
288
Pagination
29642–29653
ISSN
0021-9258
Soumis le 12 avril 2018