Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis
Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis
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DOI：
10.1182/blood-2010-02-271858
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发表时间：
2010-09-30
期刊：
影响因子：
20.3
通讯作者：
Bjorck, Lars
中科院分区：
文献类型：
--
作者：
Shannon, Oonagh;Rydengard, Victoria;Bjorck, Lars
化脓性链球菌是人类中一种重要的细菌病原体。本研究发现富组氨酸糖蛋白（HRG）是一种丰富的血浆蛋白，对化脓性S有杀伤作用。此外，化脓性S在hrg缺乏的血浆中更有效地生长，而在这种血浆中形成的凝块对细菌的捕获和杀死效果明显较差。hrg缺陷小鼠明显更容易感染化脓性链球菌。这些动物未能控制局部皮下感染，与对照组相比，脓肿形成和炎症减轻。结果，细菌传播在hrg缺陷小鼠中发生得更快，它们比对照动物更早死亡，死亡率明显更高。补充纯化HRG的HRG缺陷小鼠的表型与对照动物相同，表明缺乏HRG是导致易感性增加的原因。结果表明，HRG在炎症调节和局部细菌感染防御方面的作用是以前未被认识到的。(血。2010;116 (13):2365 - 2372)
Streptococcus pyogenesis a significant bacterial pathogen in humans. In this study, histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S pyogenes. Furthermore, S pyogenes grew more efficiently in HRG-deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG-deficient mice were strikingly more susceptible to S pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation were diminished compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG-deficient mice, and they died earlier and with a significantly higher mortality rate than control animals. HRG-deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defense at the local site of bacterial infection. (Blood. 2010;116(13):2365-2372)