(Santa Barbara, Calif.) Sepsis, the body's response to severe infections, kills more people than breast cancer, prostate cancer and HIV/AIDS combined. On average, 30 percent of those diagnosed with sepsis die.
A new study conducted by Jamey Marth, director of UC Santa Barbara's Center for Nanomedicine and professor of the Sanford-Burnham Medical Research Institute, reports a new method to increase survival in sepsis. The results appear today in the Proceedings of the National Academy of Sciences.
Building on earlier work in which Marth's team revealed the biological purpose of the Ashwell-Morell receptor (AMR) in the liver, the new discovery not only describes the AMR's protective mechanism, but also outlines a way to leverage it for therapeutic use. Sepsis often triggers widespread blood coagulation and thrombosis, which can lead to organ failure and death.
The researchers found that the AMR protects the host by the rapid removal of the prothrombotic components normally present in the bloodstream, including platelets and specific coagulation factors that contribute to the formation of blood clots. The study elucidates this mechanism of AMR function in mitigating the lethal effects of excessive blood coagulation and thrombosis in sepsis.
The key is neuraminidase, an enzyme that is present in many pathogenic microorganisms, such as Streptococcus pneumoniae, the bacteria used in this study, which remains one of the top five causes of death worldwide. Pathogens use neuraminidase to get into cells, but once the pathogen enters the bloodstream, the enzyme then remodels the surface of platelets and other glycoproteins in circulation. This remodeling signals the AMR to remove those platelets and coagulation factors before they have a chance to contribute to the lethal coagulopathy of sepsis.
"It's a highly conserved protective mechanism never before identified," said Marth, who is also Carbon Professor of Biochemis
|Contact: Julie Cohen|
University of California - Santa Barbara