Bone Morphogenetic Protein 9 Enhances Lipopolysaccharide-Induced Leukocyte Recruitment to the Vascular Endothelium.
Bone Morphogenetic Protein 9 Enhances Lipopolysaccharide-Induced Leukocyte Recruitment to the Vascular Endothelium.
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DOI：
10.4049/jimmunol.1601219
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发表时间：
2016-10-15
期刊：
影响因子：
--
通讯作者：
Morrell NW
中科院分区：
文献类型：
--
作者：
Appleby SL;Mitrofan CG;Crosby A;Hoenderdos K;Lodge K;Upton PD;Yates CM;Nash GB;Chilvers ER;Morrell NW
骨形态发生蛋白 9 (BMP9) 是一种循环生长因子，属于 TGFβ 超家族的一部分，也是血管内皮稳态的重要调节因子。先前的研究表明 BMP9 信号传导在白细胞募集到内皮细胞中发挥作用，但这种作用的方向性和潜在机制尚未阐明。在这里，我们报告说，BMP9 上调人内皮细胞中 Toll 样受体 4 (TLR4) 的表达，并且在体外流动粘附测定中，BMP9 预处理可协同增加人中性粒细胞向 LPS 刺激的人内皮单层的募集。单独的 BMP9 不会诱导中性粒细胞募集至内皮细胞。我们还表明，在 LPS 刺激的人内皮细胞中，E-选择素和 VCAM-1（而非 ICAM-1）响应 BMP9 上调。 ALK1 的 siRNA 敲低可抑制 BMP9 诱导的 TLR4 和 VCAM-1 表达，并抑制 BMP9 诱导的人中性粒细胞募集至 LPS 刺激的人内皮细胞。在小鼠急性内毒素血症模型中，BMP9 治疗还增加了肺循环内白细胞的募集。这些结果表明，虽然 BMP9 单独不会影响白细胞募集，但它会通过 TLR4、E-选择素和 VCAM-1 的增加，并最终通过增强白细胞募集，促使血管内皮在受到 LPS 攻击时产生更强烈的反应。
Bone morphogenetic protein 9 (BMP9) is a circulating growth factor that is part of the TGFβ superfamily, and an essential regulator of vascular endothelial homeostasis. Previous studies have suggested a role for BMP9 signalling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying mechanisms have not been elucidated. Here we report that BMP9 upregulates toll-like receptor 4 (TLR4) expression in human endothelial cells and that BMP9 pre-treatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay. BMP9 alone did not induce neutrophil recruitment to the endothelium. We also show that E-selectin and VCAM-1, but not ICAM-1 are upregulated in response to BMP9 in LPS-stimulated human endothelial cells. siRNA knockdown of ALK1 inhibited the BMP9-induced expression of TLR4 and VCAM-1 and inhibited BMP9-induced human neutrophil recruitment to LPS-stimulated human endothelial cells. BMP9 treatment also increased leukocyte recruitment within the pulmonary circulation in a mouse acute endotoxemia model. These results demonstrate that whilst BMP9 alone does not influence leukocyte recruitment, it primes the vascular endothelium to mount a more intense response when challenged with LPS, through an increase in TLR4, E-selectin and VCAM-1 and ultimately through enhanced leukocyte recruitment.
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影响因子：
15.9
作者：
Andonegui, G;Bonder, CS;Kubes, P
通讯作者：
Kubes, P
影响因子：
2.7
作者：
Hoodless, PA;Tsukazaki, T;Thomsen, GH
通讯作者：
Thomsen, GH
DOI：
10.1084/jem.20031076
发表时间：
2003-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Akashi S;Saitoh S;Wakabayashi Y;Kikuchi T;Takamura N;Nagai Y;Kusumoto Y;Fukase K;Kusumoto S;Adachi Y;Kosugi A;Miyake K
通讯作者：
Miyake K
影响因子：
4.4
作者：
Jeyaseelan, Samithamby;Young, Scott K.;Worthen, G. Scott
通讯作者：
Worthen, G. Scott
影响因子：
3.1
作者：
Jeyaseelan, S;Chu, HW;Worthen, GS
通讯作者：
Worthen, GS