Endothelial Heparan Sulfate Mediates Hepatic Neutrophil Trafficking and Injury during Staphylococcus aureus Sepsis
Gregory J. Golden, Alejandro Gómez Toledo, Alex Márki, James T. Sorrentino, Claire Morris, Raquel Jewel Riley, Charlotte B. Spliid, Qiongyu Chen, Ingrid Cornax, Nathan E. Lewis, Nissi Varki, Dzung Le, Johan Malmström, Christofer Karlsson, Klaus Ley, Victor Nizet, Jeffrey D. Esko
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 changes in protein composition associated with neutrophilic activity and heparin/heparan sulfate binding, all before organ damage is detectable by standard circulating liver damage markers or histology. Targeted manipulation of endothelial heparan sulfate modulates S. aureus sepsis-induced hepatotoxicity by controlling the magnitude of neutrophilic infiltration into the liver in both nonsterile and sterile injury. These data identify an important vascular glycocalyx component that impacts hepatic failure during nonsterile and sterile injury.