Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3

Maura Camozzi, Marco Rusnati, Antonella Bugatti, Barbara Bottazzi, Alberto Mantovani, Antonio Bastone, Antonio Inforzato, Silvia Vincenti, Luisa Bracci, Domenico Mastroianni, Marco Presta

Research output: Contribution to journalArticlepeer-review

Abstract

Long-pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 comprises a pentraxin-like C-terminal domain involved in complement activation via C1q interaction and an N-terminal extension with unknown functions. PTX3 binds fibroblast growth factor-2 (FGF2), inhibiting its pro-angiogenic and pro-restenotic activity. Here, retroviral transduced endothelial cells (ECs) overexpressing the N-terminal fragment PTX3-(1-178) showed reduced mitogenic activity in response to FGF2. Accordingly, purified recombinant PTX3-(1-178) binds FGF2, prevents PTX3/FGF2 interaction, and inhibits FGF2 mitogenic activity in ECs. Also, the monoclonal antibody mAb-MNB4, which recognizes the PTX3-(87-99) epitope, prevents FGF2/PTX3 interaction and abolishes the FGF2 antagonist activity of PTX3. Consistently, the synthetic peptides PTX3-(82-110) and PTX3-(97-110) bind FGF2 and inhibit the interaction of FGF2 with PTX3 immobilized to a BIAcore sensor chip, FGF2-dependent EC proliferation, and angiogenesis in vivo. Thus, the data identify a FGF2-binding domain in the N-terminal extension of PTX3 spanning the PTX3-(97-110) region, pointing to a novel function for the N-terminal extension of PTX3 and underlining the complexity of the PTX3 molecule for modular humoral pattern recognition.

Original languageEnglish
Pages (from-to)22605-22613
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number32
DOIs
Publication statusPublished - Aug 11 2006

ASJC Scopus subject areas

  • Biochemistry

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