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Publication : The Ashwell receptor mitigates the lethal coagulopathy of sepsis.

First Author  Grewal PK Year  2008
Journal  Nat Med Volume  14
Issue  6 Pages  648-55
PubMed ID  18488037 Mgi Jnum  J:136946
Mgi Id  MGI:3797421 Doi  10.1038/nm1760
Citation  Grewal PK, et al. (2008) The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 14(6):648-55
abstractText  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.
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