Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium.
Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium.
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通过肝正弦内皮对血传播病毒的快速有效清除。
DOI：
10.1371/journal.ppat.1002281
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发表时间：
2011-09
期刊：
影响因子：
6.7
通讯作者：
Anderson CL
中科院分区：
文献类型：
--
作者：
Ganesan LP;Mohanty S;Kim J;Clark KR;Robinson JM;Anderson CL
肝脏能迅速清除血液中大量的病毒，只留下一小部分感染宿主，这是每种病毒的特征。肝窦状隙的清道夫细胞也参与其中，但其机制尚不清楚。在这里，我们借用腺病毒清除的小鼠模型表明，几乎所有输注的腺病毒都被肝窦内皮细胞（LSEC）清除。使用精细的免疫荧光显微镜技术来区分固定肝脏中的巨噬细胞和内皮细胞，并通过两种不同的物理化学方法来识别病毒，我们在输注后1分钟将腺病毒主要定位于LSEC（约90%），在枯否细胞（KC）中发现约10%，在肝细胞中没有发现。电子显微镜证实了我们的结果。与之前许多声称主要清除剂是KC的工作相反，我们的结果将清除机制定位于LSEC，并将该细胞确定为抗病毒活性的关键位点。肝脏长期以来被称为身体的垃圾场，能够迅速清除血液中有害的病原体和无用的颗粒，从而保护宿主。唯一的细胞做删除已被认为是肝脏的巨噬细胞。对于较大的颗粒，如细菌，这可能是正确的。但对于病毒大小的较小颗粒或小的抗体-抗原复合物，巨噬细胞可能不是负责大部分清除的细胞。相反，我们认为，是肝脏血液循环系统的内皮细胞吸收并破坏了大部分病毒，这样做迅速（分钟）和广泛（>90%），只留下一小部分循环病毒以每种病毒特有的方式感染身体。为了测试这种可能性，我们给小鼠静脉注射了一种无害的普通感冒病毒，并通过分子和显微镜方法追踪其目的地。证实了我们的猜想，我们发现，90%的注入病毒归巢到肝脏的内皮细胞和10%的巨噬细胞。这些数据支持肝内皮在病毒清除中的独特作用，但通常未得到充分认识。
The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (∼90%), finding ∼10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity. The liver has long been known as the garbage dump of the body, capable of rapidly removing hazardous pathogens and useless particles from the blood stream, thereby protecting the host. The only cell doing the removal has been thought to be the liver's macrophages. This is likely true for larger particles such as bacteria. But for smaller particles the size of virus or small antibody-antigen complexes, macrophages are probably not the cell responsible for the bulk of removal. We suggest, rather, it is the endothelial cell of the liver's blood circulatory system that takes up and destroys the majority of virus, doing so quickly (minutes) and extensively (>90%), leaving only a small fraction of circulating virus to infect the body in ways peculiar to each virus. To test this possibility, we infused mice intravenously with a harmless common cold virus and tracked its destination by molecular and microscopy methods. Affirming our conjecture, we found that ∼90% of the infused virus homed to the endothelium of the liver and ∼10% went to its macrophages. These data support a unique role, generally underappreciated, for the liver endothelium in viral clearance.
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DOI：
10.1038/labinvest.2010.132
发表时间：
2010-12
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.2
作者：
Nakamura-Ishizu, Ayako;Morikawa, Shunichi;Ezaki, Taichi
通讯作者：
Ezaki, Taichi
影响因子：
3.6
作者：
Kawai, Y;Smedsrod, B;Wake, K
通讯作者：
Wake, K
影响因子：
4.9
作者：
Haisma, Hidde J.;Boesjes, Marije;Bellu, Anna Rita
通讯作者：
Bellu, Anna Rita
影响因子：
3.8
作者：
Lyden, TW;Anderson, CL;Robinson, JM
通讯作者：
Robinson, JM