Endothelial Heparan Sulfate Mediates Hepatic Neutrophil Trafficking and Injury during Staphylococcus aureus Sepsis

Author:

Golden Gregory J.1,Toledo Alejandro Gómez12,Marki Alex3,Sorrentino James T.45,Morris Claire1,Riley Raquel J.1,Spliid Charlotte1,Chen Qiongyu6,Cornax Ingrid7,Lewis Nathan E.789,Varki Nissi68,Le Dzung68,Malmström Johan2,Karlsson Christofer2,Ley Klaus38,Nizet Victor7810,Esko Jeffrey D.18ORCID

Affiliation:

1. Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA

2. Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden

3. La Jolla Institute for Allergy and Immunology, San Diego, California, USA

4. Department of Bioengineering, University of California, San Diego, La Jolla, California, USA

5. Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California, USA

6. Department of Pathology, University of California, San Diego, La Jolla, California, USA

7. Department of Pediatrics, University of California, San Diego, La Jolla, California, USA

8. Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA

9. Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego, La Jolla, California, USA

10. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA

Abstract

Vascular glycocalyx remodeling is critical to sepsis pathology, but the glycocalyx components that contribute to this process remain poorly characterized. This article shows that during Staphylococcus aureus sepsis, the liver vascular glycocalyx undergoes dramatic compositional changes in proteins associated with neutrophilic activity and heparin/heparan sulfate binding, all before organ damage is detectable by standard circulating liver damage markers or histology.

Funder

HHS | National Institutes of Health

UC San Diego Microbial Sciences Graduate Research Initiative

Wallenberg Foundation

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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