A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance

Blood. 2018 Feb 22;131(8):911-916. doi: 10.1182/blood-2017-06-787853. Epub 2017 Dec 27.


Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. Interestingly, in vivo clearance experiments in dual VWF-/-/Asgr1-/- mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF-/-/Asgr1-/- mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. Additionally, plasma VWF:Ag levels were significantly elevated in MGL1-/- mice compared with controls. Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asialoglycoprotein Receptor / genetics
  • Asialoglycoprotein Receptor / metabolism*
  • Asialoglycoproteins / genetics
  • Asialoglycoproteins / metabolism*
  • Cells, Cultured
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / metabolism*
  • von Willebrand Factor / physiology*


  • ASGR1 protein, human
  • Asialoglycoprotein Receptor
  • Asialoglycoproteins
  • Clec10a protein, mouse
  • Lectins, C-Type
  • Membrane Proteins
  • von Willebrand Factor
  • N-Acetylneuraminic Acid