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Stabilin Receptors Clear LPS and Control Systemic Inflammation

59 Pages Posted: 13 May 2021 Publication Status: Review Complete

See all articles by Fatima Cabral

Fatima Cabral

University of Nebraska-Lincoln

Mustafa Al-Rahem

Ohio State University (OSU) - Department of Internal Medicine

John Skaggs

University of Nebraska at Lincoln - Department of Biochemistry

Thushara A. Thomas

Ohio State University (OSU) - Department of Internal Medicine

Naresh Kumar

Ohio State University (OSU) - Department of Microbial Infection and Immunity

Qian Wu

Ohio State University (OSU) - Department of Microbial Infection and Immunity

Paolo Fadda

Ohio State University (OSU) - Comprehensive Cancer Center, Genomics Shared Resource

Lianbo Yu

Ohio State University (OSU) - Department of Biomedical Informatics

John M. Robinson (Late)

Ohio State University (OSU) - Department of Physiology and Cell Biology (deceased)

Jonghan Kim

University of Massachusetts Lowell - Department of Biomedical & Nutritional Sciences

Wael N. Jarjour

Ohio State University (OSU) - Department of Internal Medicine

Murugesan V.S Rajaram

Ohio State University (OSU) - Department of Microbial Infection and Immunity

Edward N. Harris

University of Nebraska-Lincoln

Latha P. Ganesan

Ohio State University (OSU) - Department of Internal Medicine

More...

Abstract

Lipopolysaccharides (LPS), remnants of Gram-negative bacterial cell membranes, cause lethal endotoxemia if not rapidly cleared from blood circulation.  Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanism(s).  We discovered that LPS clearance through LSEC involves endocytosis via Stabilin scavenger receptors (Stab-1 and -2) through lysosomal inactivation.  We determined that LPS was lower in the circulation of wild-type (WT) mice than Stab-1 and -2 KO mice, and endocytic uptake was higher in LSEC from WT than in Stab-1 and -2 KO.  Stab-1 and -2 KO showed enhanced systemic inflammatory cytokine production and early death compared to WT mice when exposed to LPS.  Although LSEC expresses innate immune mediator TLR4, LPS clearance does not use this functional TLR4 system.  These data suggest that Stabilin receptors facilitate the proactive clearance of LPS, and control TLR4 mediated inflammation.  The findings suggest a means of minimizing endotoxemia by optimizing Stabilin-dependent systemic LPS clearance

Keywords: LPS, liver, endotoxin, Liver sinusoidal endothelial cell, Kupffer cell, endotoxemia, systemic inflammation, endocytosis, clearance, Sepsis, gut, gram negative bacteria, innate immunity, effector functions, lysosomes, LAMP-1

Suggested Citation

Cabral, Fatima and Al-Rahem, Mustafa and Skaggs, John and Thomas, Thushara A. and Kumar, Naresh and Wu, Qian and Fadda, Paolo and Yu, Lianbo and Robinson (Late), John M. and Kim, Jonghan and Jarjour, Wael N. and Rajaram, Murugesan V.S and Harris, Edward N. and Ganesan, Latha P., Stabilin Receptors Clear LPS and Control Systemic Inflammation. Available at SSRN: https://ssrn.com/abstract=3845681 or http://dx.doi.org/10.2139/ssrn.3845681
This version of the paper has not been formally peer reviewed.

Fatima Cabral

University of Nebraska-Lincoln

Mustafa Al-Rahem

Ohio State University (OSU) - Department of Internal Medicine ( email )

Columbus, OH
United States

John Skaggs

University of Nebraska at Lincoln - Department of Biochemistry

N200 Beadle Center
1901 Vine Street
Lincoln, NE 68588-0664
United States

Thushara A. Thomas

Ohio State University (OSU) - Department of Internal Medicine ( email )

Columbus, OH
United States

Naresh Kumar

Ohio State University (OSU) - Department of Microbial Infection and Immunity

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Qian Wu

Ohio State University (OSU) - Department of Microbial Infection and Immunity

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Paolo Fadda

Ohio State University (OSU) - Comprehensive Cancer Center, Genomics Shared Resource ( email )

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Lianbo Yu

Ohio State University (OSU) - Department of Biomedical Informatics ( email )

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

John M. Robinson (Late)

Ohio State University (OSU) - Department of Physiology and Cell Biology (deceased)

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Jonghan Kim

University of Massachusetts Lowell - Department of Biomedical & Nutritional Sciences ( email )

1 University Ave
Lowell, MA 01854
United States

Wael N. Jarjour

Ohio State University (OSU) - Department of Internal Medicine ( email )

Columbus, OH
United States

Murugesan V.S Rajaram

Ohio State University (OSU) - Department of Microbial Infection and Immunity ( email )

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Edward N. Harris

University of Nebraska-Lincoln

Latha P. Ganesan (Contact Author)

Ohio State University (OSU) - Department of Internal Medicine ( email )

Columbus, OH
United States

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