| First Author | Ward SE | Year | 2018 |
| Journal | Blood | Volume | 131 |
| Issue | 8 | Pages | 911-916 |
| PubMed ID | 29282218 | Mgi Jnum | J:262174 |
| Mgi Id | MGI:6120345 | Doi | 10.1182/blood-2017-06-787853 |
| Citation | Ward SE, et al. (2018) A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. Blood 131(8):911-916 |
| abstractText | 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. alpha2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. Nevertheless, specific digestion with alpha2-3 neuraminidase (alpha2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. Interestingly, in vivo clearance experiments in dual VWF(-/-)/Asgr1(-/-) mice demonstrated enhanced clearance of alpha2-3Neu-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. |
