Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis
Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis
复制标题
尿激酶受体是细菌通过促进吞噬作用防御肺炎衍生的脓毒性类鼻疽所必需的
DOI：
10.4049/jimmunol.0901008
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
T. Poll
中科院分区：
文献类型：
--
作者：
W. Wiersinga;L. Kager;J. Hovius;G. V. D. Windt;A. F. Vos;J. Meijers;J. Roelofs;A. Dondorp;M. Levi;Nicholas P. J. Day;Nicholas P. J. Day;Sharon J. Peacock;Sharon J. Peacock;T. Poll
尿激酶受体（urokinase-type plasminogen activator receptor，uPAR），CD 87，是一种GPI锚定蛋白，在炎症和纤溶中起重要作用。革兰氏阴性细菌类鼻疽伯克霍尔德菌能够在白细胞内存活和复制，并引起类鼻疽病，这是东南亚肺炎源性社区获得性败血症的重要原因。在这项研究中，我们研究了uPAR的表达和功能，在脓毒性类鼻疽患者和实验性类鼻疽的小鼠模型。脓毒性类鼻疽患者外周血单核细胞和粒细胞以及小鼠实验性肺炎源性类鼻疽期间肺室中uPAR mRNA和表面表达增加。用B鼻内感染uPAR缺陷小鼠。假鼻疽表现出增强的生长和传播的B。与野生型小鼠相比，假鼻疽的发生与肺和肝脏炎症的增加相对应。uPAR基因敲除小鼠在接种B后，中性粒细胞向肺室的迁移显著减少。假鼻疽进一步的体外实验表明，uPAR缺陷型巨噬细胞和粒细胞显示出对B的吞噬作用明显受损。假鼻疽其他研究表明，uPAR缺乏不影响严重类鼻疽的止血和纤溶反应。这些数据表明，uPAR是至关重要的参与宿主防御由B引起的脓毒症。通过促进嗜中性粒细胞向感染的原发部位迁移，随后促进B的吞噬作用，从而抑制假鼻疽。假鼻疽
Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87), a GPI-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this study, we investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA and surface expression was increased in patients with septic melioidosis in/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with wild-type mice, corresponding with increased pulmonary and hepatic inflammation. uPAR knockout mice demonstrated significantly reduced neutrophil migration toward the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPAR-deficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils toward the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei.
影响因子：
6.4
作者：
Easton, Anna;Haque, Ashraful;Bancroft, Gregory J.
通讯作者：
Bancroft, Gregory J.
影响因子：
15.9
作者：
Yamamoto, K;Loskutoff, DJ
通讯作者：
Loskutoff, DJ