PTX3 interacts with inter-α-trypsin inhibitor: Implications for hyaluronan organization and cumulus oophorus expansion

Laura Scarchilli, Antonella Camaioni, Barbara Bottazzi, Veronica Negri, Andrea Doni, Livija Deban, Antonio Bastone, Giovanni Salvatori, Alberto Mantovani, Gregorio Siracusa, Antonietta Salustri

Research output: Contribution to journalArticlepeer-review


Pentraxin 3 (PTX3) and heavy chains (HCs) of inter-α-trypsin inhibitor (IαI) are essential for hyaluronan (HA) organization within the extracellular matrix of the cumulus oophorus, which is critical for in vivo oocyte fertilization and female fertility. In this study, we examined the possibility that these molecules interact and cooperate in this function. We show that HCs and PTX3 colocalize in the cumulus matrix and coimmunoprecipitate from cumulus matrix extracts. Coimmunoprecipitation experiments and solid-phase binding assays performed with purified human IαI and recombinant PTX3 demonstrate that their interaction is direct and not mediated by other matrix components. PTX3 does not bind to IαI subcomponent bikunin and, accordingly, bikunin does not compete for the binding of PTX3 to IαI, indicating that PTX3 interacts with IαI subcomponent HC only. Recombinant PTX3-specific N-terminal region, but not the PTX3-pentraxin C-terminal domain, showed the same ability as full-length protein to bind to HCs and to enable HA organization and matrix formation by Ptx3-/- cumulus cell oocyte complexes cultured in vitro. Furthermore, a monoclonal antibody raised against PTX3 N terminus, which inhibits PTX3/IαI interaction, also prevents recombinant full-length PTX3 from restoring a normal phenotype to in vitro-cultured Ptx3-/- cumuli. These results indicate that PTX3 directly interacts with HCs of IαI and that such interaction is essential for organizing HA in the viscoelastic matrix of cumulus oophorus, highlighting a direct functional link between the two molecules.

Original languageEnglish
Pages (from-to)30161-30170
Number of pages10
JournalJournal of Biological Chemistry
Issue number41
Publication statusPublished - Oct 12 2007

ASJC Scopus subject areas

  • Biochemistry


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