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Ashwell receptor reduces mortality during sepsis
Date:5/18/2008

nd that the pneumococcal sialidase also removes sialic acid from circulating host factors involved in blood coagulation, including platelets and a glycoprotein called von Willebrand Factor (vWF). When this occurs, the Ashwell receptor recognizes the change in the glycoprotein structure and removes those pro-coagulation factors from circulation before they can cause increased blood coagulation.

The researchers made a breakthrough when they discovered that platelet counts and vWF that are reduced during pneumococcal infection remained high and unchanged in the absence of the Ashwell receptor. Pivotal results came when mice lacking the Ashwell receptor developed severe tissue and organ damage due to increased coagulation and died at significantly higher frequency and more rapidly than expected.

This finding contradicts the prevailing notion that the low platelet count of sepsis is due to the consumption of coagulation factors caused by the pathogen and is therefore harmful, said Marth. Rather, this low platelet count is due an adaptive response by the Ashwell receptor that is beneficial by reducing tissue damage and organ failure and thereby improving the chance of survival.

More than 35 years ago, researcher Gilbert Ashwell and colleagues discovered that the liver controls the removal of proteins in the bloodstream. The Ashwell receptor also known as the hepatic asialoglycoprotein receptor was the first glycan-binding receptor, or lectin, ever discovered in animals.

The Ashwell receptor is turned on after birth, and this was a clue that it is needed for environmental and pathogenic challenges, said Marth.

This research provides a whole new way of thinking about coagulation problems in sepsis produced by pneumococcus and related pathogens said Victor Nizet, M.D., UCSD professor of pediatrics and pharmacy whose laboratory assisted in the study. Drugs designed to support the normal capabilities of the Ashwell recepto
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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