title: Inhibition of binding of lactoferrin to the human promonocyte cell line THP-1 by heparin: the role of cell surface sulphated molecules.
abstract: Lactoferrin, an iron-binding protein of the transferrin family, is a highly basic protein which interacts with many acidic molecules, including heparin proteoglycans. Such interactions may modify some of the biological properties of lactoferrin. In the present work we found that heparin caused a dose-dependent inhibition of specific binding of both human and bovine lactoferrin to human monocytic THP-1 cells. Low-affinity binding sites (Kd 500 nM) were more susceptible to inhibition by heparin than the high-affinity sites (Kd 100 nM). The effect was mediated by interaction between lactoferrin and heparin rather than by competition between heparin and lactoferrin for common binding sites on the cells. Pretreatment of cells with NaClO3 to prevent sulphation of surface glycosaminoglycans reduced lactoferrin binding, and de-N-sulphated heparin did not inhibit binding of lactoferrin to THP-1 cells. These results suggest that heparin binding and monocyte/macrophage binding by lactoferrin both involve interactions between basic regions in the N1 domain of lactoferrin and sulphate groups. The N-terminal Arg2-Arg5 sequence of human lactoferrin may be involved, but it does not seem to be the key element in these interactions.
authors.affiliation: Institute of Biochemistry, Romanian Academy, Splaiul Independentei 296, 77700 Bucharest, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Roşeanu
authors.forename: F
authors.initials: F
authors.lastname: Chelu
authors.forename: M
authors.initials: M
authors.lastname: Trif
authors.forename: C
authors.initials: C
authors.lastname: Motaş
authors.forename: J H
authors.initials: JH
authors.lastname: Brock
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D009000:Monocytes; D010472:Perchlorates; D017670:Sodium Compounds
chemical_list: D010472:Perchlorates; D017670:Sodium Compounds; D006493:Heparin; C031068:sodium perchlorate; D007781:Lactoferrin