Evaluation of the role of the asialoglycoprotein receptor in the clearance of UK-279,276 (recombinant neutrophil inhibitory factor)

Xenobiotica. 2003 Sep;33(9):945-56. doi: 10.1080/00498250310001614295.


1. UK-279,276 or recombinant neutrophil inhibitory factor (rNIF) is a glycoprotein that has been investigated as an intravenous treatment for stroke. Previous data indicate that the asialoglycoprotein receptor (ASGPR) in the liver might have a role in the uptake and clearance of UK-279,276 from plasma in rats and dogs. 2. Biliary elimination of sialo UK-279,276 can be inhibited by the co-administration of asialo fetuin, a known substrate for ASGPR. These data are in keeping with sialo UK-279,276 being cleared by ASGPR. 3. In vitro experiments have demonstrated that asialo UK-279,276 (Sialo UK-279,276 treated to remove the sialic acid residues present on the glycans) shows a significantly greater uptake in rat, dog and human precision-cut liver slices than the sialylated protein. The addition of asialo fetuin to precision-cut liver slice incubations (rat, dog and man) containing asialo UK-279,276 reduced the uptake to levels similar to those seen for the sialylated protein. These data support the potential role of the ASGPR in the clearance of UK-279,276 in rat, dog and man.

MeSH terms

  • Animals
  • Asialoglycoprotein Receptor / metabolism*
  • Bile / metabolism
  • Bile Ducts / metabolism
  • Dogs
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Glycoproteins / pharmacokinetics*
  • Helminth Proteins / pharmacokinetics*
  • Humans
  • In Vitro Techniques
  • Liver / anatomy & histology
  • Liver / cytology
  • Liver / metabolism
  • Membrane Proteins / pharmacokinetics*
  • Rats
  • Rats, Inbred F344
  • Recombinant Proteins / pharmacokinetics
  • Species Specificity


  • Asialoglycoprotein Receptor
  • Fluorescent Dyes
  • Glycoproteins
  • Helminth Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • UK279276
  • NIF protein, Ancylostoma caninum
  • Fluorescein-5-isothiocyanate