Stabilin receptors clear LPS and control systemic inflammation

Summary: Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabil...

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Autores principales:	Fatima Cabral, Mustafa Al-Rahem, John Skaggs, Thushara A. Thomas, Naresh Kumar, Qian Wu, Paolo Fadda, Lianbo Yu, John M. Robinson, Jonghan Kim, Ekta Pandey, Xinghui Sun, Wael N. Jarjour, Murugesan V.S. Rajaram, Edward N. Harris, Latha P. Ganesan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Molecular biology Immune response Science Q
Acceso en línea:	https://doaj.org/article/209b703b99394a00aadccb8cd283ebee
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spelling	oai:doaj.org-article:209b703b99394a00aadccb8cd283ebee2021-11-20T05:10:07ZStabilin receptors clear LPS and control systemic inflammation2589-004210.1016/j.isci.2021.103337https://doaj.org/article/209b703b99394a00aadccb8cd283ebee2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013067https://doaj.org/toc/2589-0042Summary: Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory LPS clearance, LPS uptake and endocytosis by LSEC, and cytokine production. These data indicate that (1) Stab1 receptor primarily facilitates the proactive clearance of LPS and limits TLR4-mediated inflammation and (2) TLR4 and Stab1 are functionally opposing LPS receptors. These findings suggest that endotoxemia can be controlled by optimizing LPS clearance by Stab1.Fatima CabralMustafa Al-RahemJohn SkaggsThushara A. ThomasNaresh KumarQian WuPaolo FaddaLianbo YuJohn M. RobinsonJonghan KimEkta PandeyXinghui SunWael N. JarjourMurugesan V.S. RajaramEdward N. HarrisLatha P. GanesanElsevierarticleBiological sciencesMolecular biologyImmune responseScienceQENiScience, Vol 24, Iss 11, Pp 103337- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Molecular biology Immune response Science Q
spellingShingle	Biological sciences Molecular biology Immune response Science Q Fatima Cabral Mustafa Al-Rahem John Skaggs Thushara A. Thomas Naresh Kumar Qian Wu Paolo Fadda Lianbo Yu John M. Robinson Jonghan Kim Ekta Pandey Xinghui Sun Wael N. Jarjour Murugesan V.S. Rajaram Edward N. Harris Latha P. Ganesan Stabilin receptors clear LPS and control systemic inflammation
description	Summary: Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory LPS clearance, LPS uptake and endocytosis by LSEC, and cytokine production. These data indicate that (1) Stab1 receptor primarily facilitates the proactive clearance of LPS and limits TLR4-mediated inflammation and (2) TLR4 and Stab1 are functionally opposing LPS receptors. These findings suggest that endotoxemia can be controlled by optimizing LPS clearance by Stab1.
format	article
author	Fatima Cabral Mustafa Al-Rahem John Skaggs Thushara A. Thomas Naresh Kumar Qian Wu Paolo Fadda Lianbo Yu John M. Robinson Jonghan Kim Ekta Pandey Xinghui Sun Wael N. Jarjour Murugesan V.S. Rajaram Edward N. Harris Latha P. Ganesan
author_facet	Fatima Cabral Mustafa Al-Rahem John Skaggs Thushara A. Thomas Naresh Kumar Qian Wu Paolo Fadda Lianbo Yu John M. Robinson Jonghan Kim Ekta Pandey Xinghui Sun Wael N. Jarjour Murugesan V.S. Rajaram Edward N. Harris Latha P. Ganesan
author_sort	Fatima Cabral
title	Stabilin receptors clear LPS and control systemic inflammation
title_short	Stabilin receptors clear LPS and control systemic inflammation
title_full	Stabilin receptors clear LPS and control systemic inflammation
title_fullStr	Stabilin receptors clear LPS and control systemic inflammation
title_full_unstemmed	Stabilin receptors clear LPS and control systemic inflammation
title_sort	stabilin receptors clear lps and control systemic inflammation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/209b703b99394a00aadccb8cd283ebee
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_version_	1718419529784098816

Stabilin receptors clear LPS and control systemic inflammation

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