title: Interaction of human lactoferrin with cell adhesion molecules through RGD motif elucidated by lactoferrin-binding epitopes.
abstract: Lactoferrin (LF) is an iron-binding secretory protein, which is distributed in the secondary granules of polynuclear lymphocytes as well as in the milk produced by female mammals. Although it has multiple functions, for example antimicrobial, immunomodulatory, antiviral, and anti-tumor metastasis activities, the receptors responsible for these activities are not fully understood. In this study, the binding epitopes for human LF were first isolated from a hexameric random peptide library displayed on T7 phage. Interestingly, two of the four isolated peptides had a representative cell adhesion motif, Arg-Gly-Asp (RGD), implying that human LF interacts with proteins with the RGD motif. We found that human LF bound to the RGD-containing human extracellular matrix proteins, fibronectin and vitronectin. Furthermore, human LF inhibited cell adhesion to these matrix proteins in a concentration-dependent manner but not to the RGD-independent cell adhesion molecule like laminin or collagen. These results indicate that a function of human LF is to block the various interactions between the cell surface and adhesion molecules. This may explain the multifunctionality of LF.
authors.affiliation: Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mori
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugimura
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides; D011485:Protein Binding
chemical_list: D015815:Cell Adhesion Molecules; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D007781:Lactoferrin