Lactoferrin binding to heparan sulfate proteoglycans and the LDL receptor-related protein. Further evidence supporting the importance of direct binding of remnant lipoproteins to HSPG

Arterioscler Thromb. 1994 Dec;14(12):2025-31. doi: 10.1161/01.atv.14.12.2025.

Abstract

Bovine lactoferrin inhibits the clearance of remnant lipoproteins from the plasma and competes with the cell-surface binding of apolipoprotein (apo) E-enriched remnants. We established that lactoferrin inhibits remnant binding and uptake by interacting with both heparan sulfate proteoglycans (HSPG) and the low-density lipoprotein receptor-related protein (LRP). The binding of 125I-lactoferrin was inhibited 45% to 60% in HepG2 hepatocytes and wild-type Chinese hamster ovary (CHO) cells treated with heparinase to remove HSPG. In mutant CHO cells (pgsD-677) lacking HSPG, the level of 125I-lactoferrin binding was approximately 50% that seen with wild-type CHO cells; thus, about one half of lactoferrin binding appears to be mediated through cell-surface HSPG. A significant fraction of the residual binding of the lactoferrin appears to be mediated through the LRP. The 39-kd protein known to bind to the LRP and to block ligand interaction inhibited 125I-lactoferrin degradation in wild-type CHO cells by 60% to 65%. The addition of the 39-kd protein plus heparinase treatment reduced the binding by 85% to 90% (this combination blocks direct interaction with both the LRP and HSPG). However, it was also shown that the 39-kd protein bound to HSPG and the LRP. Heparinase treatment of wild-type CHO cells decreased the binding of the 125I-39-kd protein by approximately 40%, and the mutant CHO cells lacking HSPG bound half as much 125I-39-kd protein as wild-type CHO cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Chylomicrons / metabolism
  • Cricetinae
  • Heparitin Sulfate / metabolism*
  • Lactoferrin / metabolism*
  • Lipoproteins, VLDL / metabolism
  • Liver / cytology
  • Liver / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Rabbits
  • Receptors, Immunologic / metabolism*
  • Receptors, LDL / metabolism*
  • alpha-Macroglobulins / metabolism*

Substances

  • Chylomicrons
  • Lipoproteins, VLDL
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Immunologic
  • Receptors, LDL
  • alpha-Macroglobulins
  • Heparitin Sulfate
  • Lactoferrin