Department of Anesthesiology, University of Toronto, Ontario, Canada.
Antiviral Res. 2012 Jan;93(1):2-15. doi: 10.1016/j.antiviral.2011.10.019. Epub 2011 Nov 2.
A dysregulated immune response and functional immunosuppression have been considered the major mechanisms of the bacterial sepsis syndrome. More recently, the loss of endothelial barrier function and resultant microvascular leak have been found to be a key determinant of the pathogenesis of bacterial sepsis. Whether a similar paradigm applies to systemic viral syndromes is not known. Answering this question has far-reaching implications for the development of future anti-viral therapeutic strategies. In this review, we provide an overview of the structure and function of the endothelium and how its barrier integrity is compromised in bacterial sepsis. The various in vitro and in vivo methodologies available to investigate vascular leak are reviewed. Emphasis is placed on the advantages and limitations of cell culture techniques, which represent the most commonly used methods. Within this context, we appraise recent studies of three viruses - hantavirus, human herpes virus 8 and dengue virus - that suggest microvascular leak may play a role in the pathogenesis of these viral infections. We conclude with a discussion of how endothelial barrier breakdown may occur in other viral infections such as H5N1 avian influenza virus.
免疫反应失调和功能免疫抑制被认为是细菌性败血症综合征的主要机制。最近，发现内皮屏障功能的丧失和由此产生的微血管渗漏是细菌性败血症发病机制的关键决定因素。这种类似的模式是否适用于全身病毒性综合征尚不清楚。回答这个问题对未来抗病毒治疗策略的发展具有深远的意义。在这篇综述中，我们概述了内皮的结构和功能，以及其屏障完整性在细菌性败血症中是如何受到损害的。我们回顾了可用于研究血管渗漏的各种体外和体内方法。重点介绍了细胞培养技术的优势和局限性，细胞培养技术是最常用的方法。在这种情况下，我们评估了三种病毒（汉坦病毒、人类疱疹病毒 8 型和登革热病毒）的最新研究，这些研究表明微血管渗漏可能在这些病毒感染的发病机制中起作用。最后，我们讨论了内皮屏障破坏如何在其他病毒感染（如 H5N1 禽流感病毒）中发生。
