Journal
NATURE MEDICINE
Volume 14, Issue 6, Pages 648-655Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1760
Keywords
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NHLBI NIH HHS [P01 HL057345, P01 HL057345-100001, P01 HL057345-110006, P01 HL057345-109004, HL-57345] Funding Source: Medline
- NIAID NIH HHS [AI-051796] Funding Source: Medline
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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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