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

J Biol Chem 2006 Aug 12;281(32):22605-13. Epub 2006 Jun 12.

Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, 25123 Brescia, Italy.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M601023200DOI Listing
August 2006

Publication Analysis

Top Keywords

pattern recognition
12
n-terminal extension
12
ptx3
9
extension ptx3
8
mitogenic activity
8
soluble pattern
8
recognition receptor
8
fgf2
7
antibody mab-mnb4
4
inhibits fgf2
4
fgf2 mitogenic
4
monoclonal antibody
4
activity ecs
4
ecs monoclonal
4
antagonist activity
4
prevents fgf2/ptx3
4
fgf2/ptx3 interaction
4
interaction abolishes
4
abolishes fgf2
4
epitope prevents
4

Altmetric Statistics

Similar Publications