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Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice

The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupff...

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Autores principales: Jiang, Yizhi, Tang, Yaqiong, Hoover, Christopher, Kondo, Yuji, Huang, Dongping, Restagno, Damien, Shao, Bojing, Gao, Liang, Michael McDaniel, J., Zhou, Meixiang, Silasi-Mansat, Robert, McGee, Samuel, Jiang, Miao, Bai, Xia, Lupu, Florea, Ruan, Changgeng, Marth, Jamey D., Wu, Depei, Han, Yue, Xia, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564511/
https://www.ncbi.nlm.nih.gov/pubmed/33993195
http://dx.doi.org/10.1038/s41418-021-00797-w
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author Jiang, Yizhi
Tang, Yaqiong
Hoover, Christopher
Kondo, Yuji
Huang, Dongping
Restagno, Damien
Shao, Bojing
Gao, Liang
Michael McDaniel, J.
Zhou, Meixiang
Silasi-Mansat, Robert
McGee, Samuel
Jiang, Miao
Bai, Xia
Lupu, Florea
Ruan, Changgeng
Marth, Jamey D.
Wu, Depei
Han, Yue
Xia, Lijun
author_facet Jiang, Yizhi
Tang, Yaqiong
Hoover, Christopher
Kondo, Yuji
Huang, Dongping
Restagno, Damien
Shao, Bojing
Gao, Liang
Michael McDaniel, J.
Zhou, Meixiang
Silasi-Mansat, Robert
McGee, Samuel
Jiang, Miao
Bai, Xia
Lupu, Florea
Ruan, Changgeng
Marth, Jamey D.
Wu, Depei
Han, Yue
Xia, Lijun
author_sort Jiang, Yizhi
collection PubMed
description The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupffer cells express a C-type lectin receptor, CLEC4F, that recognizes desialylated glycans with an unclear in vivo role in mediating platelet destruction. In this study, we generated a CLEC4F-deficient mouse model (Clec4f(−/−)) and found that CLEC4F was specifically expressed by Kupffer cells. Using the Clec4f(−/−) mice and a newly generated platelet-specific reporter mouse line, we revealed a critical role for CLEC4F on Kupffer cells in mediating destruction of desialylated platelets in the liver in vivo. Platelet clearance experiments and ultrastructural analysis revealed that desialylated platelets were phagocytized predominantly by Kupffer cells in a CLEC4F-dependent manner in mice. Collectively, these findings identify CLEC4F as a Kupffer cell receptor important for the destruction of desialylated platelets induced by bacteria-derived neuraminidases, which provide new insights into the pathogenesis of thrombocytopenia in disease conditions such as sepsis.
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spelling pubmed-85645112021-11-16 Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice Jiang, Yizhi Tang, Yaqiong Hoover, Christopher Kondo, Yuji Huang, Dongping Restagno, Damien Shao, Bojing Gao, Liang Michael McDaniel, J. Zhou, Meixiang Silasi-Mansat, Robert McGee, Samuel Jiang, Miao Bai, Xia Lupu, Florea Ruan, Changgeng Marth, Jamey D. Wu, Depei Han, Yue Xia, Lijun Cell Death Differ Article The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupffer cells express a C-type lectin receptor, CLEC4F, that recognizes desialylated glycans with an unclear in vivo role in mediating platelet destruction. In this study, we generated a CLEC4F-deficient mouse model (Clec4f(−/−)) and found that CLEC4F was specifically expressed by Kupffer cells. Using the Clec4f(−/−) mice and a newly generated platelet-specific reporter mouse line, we revealed a critical role for CLEC4F on Kupffer cells in mediating destruction of desialylated platelets in the liver in vivo. Platelet clearance experiments and ultrastructural analysis revealed that desialylated platelets were phagocytized predominantly by Kupffer cells in a CLEC4F-dependent manner in mice. Collectively, these findings identify CLEC4F as a Kupffer cell receptor important for the destruction of desialylated platelets induced by bacteria-derived neuraminidases, which provide new insights into the pathogenesis of thrombocytopenia in disease conditions such as sepsis. Nature Publishing Group UK 2021-05-15 2021-11 /pmc/articles/PMC8564511/ /pubmed/33993195 http://dx.doi.org/10.1038/s41418-021-00797-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jiang, Yizhi
Tang, Yaqiong
Hoover, Christopher
Kondo, Yuji
Huang, Dongping
Restagno, Damien
Shao, Bojing
Gao, Liang
Michael McDaniel, J.
Zhou, Meixiang
Silasi-Mansat, Robert
McGee, Samuel
Jiang, Miao
Bai, Xia
Lupu, Florea
Ruan, Changgeng
Marth, Jamey D.
Wu, Depei
Han, Yue
Xia, Lijun
Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title_full Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title_fullStr Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title_full_unstemmed Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title_short Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice
title_sort kupffer cell receptor clec4f is important for the destruction of desialylated platelets in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564511/
https://www.ncbi.nlm.nih.gov/pubmed/33993195
http://dx.doi.org/10.1038/s41418-021-00797-w
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