Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen.

Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen.
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单核细胞对细胞内病原体的炎症反应的流体动力调节。

DOI:
10.1371/journal.pone.0014492
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发表时间:
2011-01-07
期刊:
影响因子:
3.7
通讯作者:
Ramasubramanian AK
Ramasubramanian AK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Evani SJ;Murthy AK;Mareedu N;Montgomery RK;Arulanandam BP;Ramasubramanian AK

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全身性细菌感染引起炎症反应,促进急性或慢性并发症,如败血症,关节炎或动脉粥样硬化。感兴趣的是,循环中的细胞经历流体动力学剪切力,其已被证明是脉管系统中细胞功能的有效调节剂,并且在维持组织稳态中起重要作用。在这项研究中,我们已经检查了由于血液流动的剪切力在调节细胞对感染的炎症反应中的作用。使用体外模型,我们分析了生理水平的切应力对感染衣原体的单核细胞的炎症反应的影响,衣原体是一种细胞内病原体,可引起支气管炎,并与动脉粥样硬化的发展有关。我们发现衣原体感染改变了单核细胞的形态,并触发促炎细胞因子TNF-α、IL-8、IL-1β和IL-6的释放。我们还发现,衣原体感染的单核细胞暴露于短时间的动脉切应力显着增强细胞因子的分泌在一个时间依赖性的方式和表面粘附分子ICAM-1的表达。作为一个功能性的结果,感染和剪切应力增加单核细胞粘附到内皮细胞的流动和血小板的活化和聚集。总的来说,我们的研究表明,剪切应力增强单核细胞对感染的炎症反应,表明机械力可能有助于疾病的病理生理学。这些结果为我们理解全身感染和炎症提供了一个新的视角。
Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation.
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