Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney
Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney
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DOI：
10.1152/ajprenal.00414.2005
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
Dagher, PC
中科院分区：
文献类型：
--
作者：
El-Achkar, TM;Huang, XP;Dagher, PC
Toll样受体（TLR）现在被认为是先天免疫系统细胞上微生物病原体的主要受体。最近，TLR也在包括肾脏在内的许多器官中被鉴定。然而，这些肾脏TLR的细胞分布和作用在很大程度上仍然未知。在本文中，我们研究了TLR 4的表达在盲肠结扎穿孔（CLP）脓毒症模型在Sprague-Dawley大鼠利用荧光显微镜。在假手术动物中，TLR 4主要在Tamm-Horsfall蛋白（THP）阳性小管中表达。在CLP动物中，TLR 4表达在所有小管（近端和远端）、肾小球和肾血管系统中显著增加。染色显示在所有小管中的强顶端分布。一个中等强度较低的细胞信号共定位部分与高尔基体。此外，脓毒症大鼠的肾脏显示CD 14和THP的表达增加。它们各自与TLR 4强烈共定位，尽管在不同的管段中。我们还成像后，荧光脂多糖（LPS）注射活脓毒症动物的肾脏与双光子显微镜。在10分钟内，在一些近端小管的刷状缘处观察到LPS。在60分钟内，LPS在近端小管中完全是细胞质。相反，远端小管显示无LPS摄取。我们的结论是，TLR 4，CD 14，和THP具有特定的肾细胞和肾小管表达模式，明显受到脓毒症的影响。全身内毒素可以自由进入这些蛋白质存在的肾小管和细胞部位。因此，局部表达的TLR和其他相互作用的蛋白质可能会调节肾脏对全身性脓毒症的反应。
Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules ( proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.