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The Ashwell receptor mitigates the lethal coagulopathy of sepsis
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Journal Article
The Ashwell receptor mitigates the lethal coagulopathy of sepsis
2008
Overview
The Ashwell receptor, the major lectin of hepatocytes, rapidly clears from blood circulation glycoproteins bearing glycan ligands that include galactose and
N
-acetylgalactosamine. This asialoglycoprotein receptor activity remains a key factor in the development and administration of glycoprotein pharmaceuticals, yet a biological purpose of the Ashwell receptor has remained elusive. We have identified endogenous ligands of the Ashwell receptor as glycoproteins and regulatory components in blood coagulation and thrombosis that include von Willebrand factor (vWF) and platelets. The Ashwell receptor normally modulates vWF homeostasis and is responsible for thrombocytopenia during systemic
Streptococcus pneumoniae
infection by eliminating platelets desialylated by the bacterium's neuraminidase. Hemostatic adaptation by the Ashwell receptor moderates the onset and severity of disseminated intravascular coagulation during sepsis and improves the probability of host survival.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Asialoglycoprotein Receptor - blood
/ Asialoglycoprotein Receptor - genetics
/ Asialoglycoprotein Receptor - metabolism
/ Asialoglycoproteins - pharmacokinetics
/ Biomedical and Life Sciences
/ Blood Coagulation Disorders - blood
/ Blood Coagulation Disorders - pathology
/ Blood Platelets - metabolism
/ Blood Platelets - microbiology
/ Complications and side effects
/ Fluorescent Antibody Technique, Indirect
/ Humans
/ Lectins
/ Ligands
/ Liver
/ Metabolic Clearance Rate - genetics
/ Mice
/ Mutation
/ Pneumococcal Infections - metabolism
/ Pneumococcal Infections - pathology
/ Sepsis
/ Thrombocytopenia - microbiology
