The Pathogen Receptor Liver and Lymph Node Sinusoidal Endotelial Cell C-Type Lectin Is Expressed in Human Kupffer Cells and Regulated by PU.1
The Pathogen Receptor Liver and Lymph Node Sinusoidal Endotelial Cell C-Type Lectin Is Expressed in Human Kupffer Cells and Regulated by PU.1
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DOI：
10.1002/hep.22678
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发表时间：
2009-01-01
期刊：
影响因子：
13.5
通讯作者：
Corbi, Angel L.
中科院分区：
文献类型：
--
作者：
Dominguez-Soto, Angeles;Aragoneses-Fenoll, Laura;Corbi, Angel L.
Human LSECtin （Human liver and lymph node sinusoidal endothelial cell C-type lectin, CLEC4G）是一种编码在L-SIGN/DC-SIGN/CD23基因簇中的c型凝集素。LSECtin是埃博拉病毒和SARS冠状病毒的病原体附着因子，白细胞介素-4可诱导其在单核细胞和巨噬细胞上表达。虽然LSECtin是肝脏和淋巴结内皮细胞特异性分子，但在MUTZ-3树突样细胞系中可以检测到mRNA和蛋白水平的LSECtin，对人肝脏的免疫组化分析显示，LSECtin存在于共表达髓系标志物CD68的Kupffer细胞中。通过分析人LSECtin基因的近端调控区进一步证实了LSECtin在髓细胞中的表达，该区域在LSECtin +髓细胞中活性最大，且含有高度保守的pu .1结合位点。PU.1与造血限制性转录因子（Myb, RUNX3）协同反激活LSECtin调控区，并被发现与LSECtin近端启动子组成性结合。此外，通过使用小干扰RNA敲低PU.1导致THP-1和单核细胞来源的树突状细胞中LSECtin mRNA水平下降，从而证实PU.1参与了凝集素的髓系表达。结论：LSECtin可在肝髓细胞中表达，其表达依赖于PU.1转录因子。(肝脏病学49:287 2009;296)。
Human LSECtin (liver and lymph node sinusoidal endothelial cell C-type lectin, CLEC4G) is a C-type lectin encoded within the L-SIGN/DC-SIGN/CD23 gene cluster. LSECtin acts as a pathogen attachment factor for Ebolavirus and the SARS coronavirus, and its expression can be induced by interleukin-4 on monocytes and macrophages. Although reported as a liver and lymph node sinusoidal endothelial cell-specific molecule, LSECtin could be detected in the MUTZ-3 dendritic-like cell line at the messenger RNA (mRNA) and protein level, and immunohistochemistry analysis on human liver revealed its presence in Kupffer cells coexpressing the myeloid marker CD68. The expression of LSECtin in myeloid cells was further corroborated through the analysis of the proximal regulatory region of the human LSECtin gene, whose activity was maximal in LSECtin + myeloid cells, and which contains a highly conserved PU.1-binding site. PU.1 transactivated the LSECtin regulatory region in collaboration with hematopoietic-restricted transcription factors (Myb, RUNX3), and was found to bind constitutively to the LSECtin proximal promoter. Moreover, knockdown of PU.1 through the use of small interfering RNA led to a decrease in LSECtin mRNA levels in THP-1 and monocyte-derived dendritic cells, thus confirming the involvement of PU.1 in the myeloid expression of the lectin. Conclusion: LSECtin is expressed by liver myeloid cells, and its expression is dependent on the PU.1 transcription factor. (HEPATOLOGY 2009;49:287-296.)