title: 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.
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)
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, San Francisco, CA 94141-9100.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Ji
authors.forename: R W
authors.initials: RW
authors.lastname: Mahley
mesh_terms: D000818:Animals; D016466:CHO Cells; D002914:Chylomicrons / Q000378:metabolism; D006224:Cricetinae; D006497:Heparan Sulfate / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D002914:Chylomicrons; D006497:Heparan Sulfate; D007781:Lactoferrin; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000511:alpha-Macroglobulins