Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis
Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis
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DOI：
10.1182/blood-2003-10-3433
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发表时间：
2004-07-01
期刊：
影响因子：
20.3
通讯作者：
Presta, M
中科院分区：
文献类型：
--
作者：
Rusnati, M;Camozzi, M;Presta, M
长五肽PTX3是一种可溶性的模式识别受体，由单核细胞和内皮细胞产生，在炎症中发挥非多余的作用。一些病理情况的特点是局部产生PTX3和血管生成成纤维细胞生长因子-2(FGF2)。固相结合分析表明，PTX3与FGF2有很高的亲和力，但不能与一组细胞因子和生长因子结合，包括FGF1、FGF4和FGF8。因此，PTX3阻止I-125-FGF2与内皮细胞受体结合，从而特异性地抑制FGF2诱导的增殖。PTX3还可抑制内源性FGF2在损伤内皮细胞单层上发挥的促动作用。此外，PTX3基因在FGF2转化的内皮细胞中的转导抑制了其依赖于FGF2的体外自分泌增殖和形态发生，以及当注射到裸鼠体内时产生血管损伤的能力。最后，PTX3抑制了FGF2在鸡胚绒毛尿囊膜中触发的新生血管，但对生理性血管生成没有影响。相反，短的五角蛋白C反应蛋白是一个很差的FGF2配体/拮抗剂。这些结果建立了五肽超家族的一个成员与生长因子的选择性结合。PTX3/FGF2相互作用可能在炎症、先天免疫和/或肿瘤转化等多种生理病理条件下调节血管生成。(C)2004年，由美国血液病学会提供。
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 I-125-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. (C) 2004 by The American Society of Hematology.