Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors
Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors
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DOI：
10.1016/j.micinf.2007.08.005
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发表时间：
2007-10-01
影响因子：
5.8
通讯作者：
Matsushita, Kenji
中科院分区：
文献类型：
--
作者：
Inomata, Megumi;Into, Takeshi;Matsushita, Kenji
牙龈痛牙龈卟啉单胞菌（Porphyromonasgingivalis）的半胱氨酸蛋白酶是牙周病中重要的毒力因子。我们发现，精氨酸特异性牙龈菌蛋白酶A（RgpA）增加血管内皮细胞对牙龈卟啉单胞菌脂多糖（LPS）和牙龈卟啉单胞菌全细胞的反应性，以通过蛋白酶激活受体（PAR）和磷脂酶C（PLC）γ诱导增强的IL-8产生。因此，我们研究是否RgpA诱导的增强细胞活化是通过胞吐的韦伯-帕拉德体（WPB），因为他们存储血管活性物质介导的。RgpA迅速激活PAR和PLC γ依赖的WPB胞吐作用。另外，WPB的一种物质血管生成素（Ang）-2可促进牙龈卟啉单胞菌LPS产生IL-8，提示Ang-2介导了RgpA诱导的增强的细胞反应。因此，我们提出了一个新的作用，RgpA诱导的促炎事件通过PAR介导的WPB胞吐，这可能是一个重要的步骤，增强内皮细胞对牙龈卟啉单胞菌的反应。(c)2007年，Elsevier Masson SAS。All rights reserved.
Gingipains. cysteine proteases derived from Porphyromonas gingivalis, are important virulence factors in periodontal diseases. We found that arginine-specific gingipain A (RgpA) increased the responsiveness of vascular endothelial cells to P. gingivalis lipopolysaccharides (LPS) and P. gingivalis whole cells to induce enhanced IL-8 production through protease-activated receptors (PARs) and phospholipase C (PLC) gamma. We therefore investigated whether RgpA-induced enhanced cell activation is mediated through exocytosis of Weibel-Palade bodies (WPBs) because they store vasoactive substances. RgpA rapidly activated PAR- and PLC gamma-dependent WPB exocytosis. In addition, angiopoietin (Ang)-2, a substance of WPB, enhanced IL-8 production by P. gingivalis LPS, suggesting that Ang-2 mediates the RgpA-induced enhanced cell responses. Thus, we propose a novel role for RgpA in induction of a proinflammatory event through PAR-mediated WPB exocytosis, which may be an important step for enhanced endothelial responses to P. gingivalis. (c) 2007 Elsevier Masson SAS. All rights reserved.