Journal
HEPATOLOGY
Volume 49, Issue 1, Pages 287-296Publisher
WILEY
DOI: 10.1002/hep.22678
Keywords
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Categories
Funding
- Ministerio de Educacion y Ciencia [SAF2005-0021, GEN2003-20649-C06-011NAC]
- Ministerio de Sanidad y Consumo
- Instituto de Salud Carlos III (Spanish Network for Research in Infectious Diseases) [REIPI RD06/0008/00012]
- Red de SIDA [RD06/0006/1016]
- Fundacion para la Investigacion y Prevencion del SIDA en Espana [FIPSF 36663107]
- Fundacion Mutua Madrilena
- Ministerio de Educacion y Ciencia, Spain [BES2004-4405]
- Instituto de Salud Carlos III
- [SAF2006-03191]
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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.)
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