Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis

• Published in: Blood Vol. 104; no. 1; pp. 92 - 99
• Main Authors: Rusnati, Marco, Camozzi, Maura, Moroni, Emanuela, Bottazzi, Barbara, Peri, Giuseppe, Indraccolo, Stefano, Amadori, Alberto, Mantovani, Alberto, Presta, Marco
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.07.2004; The Americain Society of Hematology
• Subjects: Angiogenesis Inhibitors - genetics; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - physiology; Animals; Autocrine Communication - drug effects; Autocrine Communication - physiology; Biological and medical sciences; Blood coagulation. Blood cells; C-Reactive Protein - chemistry; C-Reactive Protein - genetics; C-Reactive Protein - pharmacology; C-Reactive Protein - physiology; Cattle; Cell Division - drug effects; Cell Division - physiology; Cell Line; Chick Embryo; CHO Cells; Cricetinae; Cricetulus; Cytokines - metabolism; Endothelial Cells - cytology; Endothelial Cells - metabolism; Fibroblast Growth Factor 2 - antagonists & inhibitors; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Heparan Sulfate Proteoglycans - metabolism; Humans; Mice; Mice, Nude; Mitogens - metabolism; Molecular and cellular biology; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Radioligand Assay; Receptors, Fibroblast Growth Factor - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Serum Amyloid P-Component - chemistry; Serum Amyloid P-Component - genetics; Serum Amyloid P-Component - pharmacology; Serum Amyloid P-Component - physiology; Human; Fibroblast growth factor; Endothelial cell; Angiogenic factor; Cytokine; Molecular interaction; Pentraxine PTX3; Angiogenesis; Acute phase protein; Polypeptide; Animal; Inhibitor; Neovascularization; Growth factor; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-10-3433

The long pentraxin PTX3 is a soluble pattern recognition receptor produced by monocytes and endothelial cells that plays a nonredundant role in inflammation. Several pathologic conditions are characterized by local production of both PTX3 and the angiogenic fibroblast growth factor-2 (FGF2). Here, solid-phase binding assays demonstrated that PTX3 binds with high affinity to FGF2 but not to a panel of cytokines and growth factors, including FGF1, FGF4, and FGF8. Accordingly, PTX3 prevented 125I-FGF2 binding to endothelial cell receptors, leading to specific inhibition of FGF2-induced proliferation. PTX3 hampered also the motogenic activity exerted by endogenous FGF2 on a wounded endothelial cell monolayer. Moreover, PTX3 cDNA transduction in FGF2-transformed endothelial cells inhibited their autocrine FGF2-dependent proliferation and morphogenesis in vitro and their capacity to generate vascular lesions when injected in nude mice. Finally, PTX3 suppressed neovascularization triggered by FGF2 in the chick embryo chorioallantoic membrane with no effect on physiologic angiogenesis. In contrast, the short pentraxin C-reactive protein was a poor FGF2 ligand/antagonist. These results establish the selective binding of a member of the pentraxin superfamily to a growth factor. PTX3/FGF2 interaction may modulate angiogenesis in various physiopathologic conditions driven by inflammation, innate immunity, and/or neoplastic transformation.