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 language | English |
|---|---|
| Pages (from-to) | 22605-22613 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 281 |
| Issue number | 32 |
| DOIs | |
| Publication status | Published - Aug 11 2006 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3. / Camozzi, Maura; Rusnati, Marco; Bugatti, Antonella; Bottazzi, Barbara; Mantovani, Alberto; Bastone, Antonio; Inforzato, Antonio; Vincenti, Silvia; Bracci, Luisa; Mastroianni, Domenico; Presta, Marco.
In: Journal of Biological Chemistry, Vol. 281, No. 32, 11.08.2006, p. 22605-22613.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3
AU - Camozzi, Maura
AU - Rusnati, Marco
AU - Bugatti, Antonella
AU - Bottazzi, Barbara
AU - Mantovani, Alberto
AU - Bastone, Antonio
AU - Inforzato, Antonio
AU - Vincenti, Silvia
AU - Bracci, Luisa
AU - Mastroianni, Domenico
AU - Presta, Marco
PY - 2006/8/11
Y1 - 2006/8/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33747336999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747336999&partnerID=8YFLogxK
U2 - 10.1074/jbc.M601023200
DO - 10.1074/jbc.M601023200
M3 - Article
C2 - 16769728
AN - SCOPUS:33747336999
VL - 281
SP - 22605
EP - 22613
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 32
ER -