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.
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)
Ji
Z S
ZS
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, San Francisco, CA 94141-9100.
Mahley
R W
RW
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*
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