title: Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects.
abstract: Lactoferrin (Lf), a multifunctional protein of the innate immune response, seems to act as a permeabilizing agent of Gram negative bacteria, apparently due to its interaction with enterobacterial lipopolysaccharide (LPS) on the bacterial surface. In both human and bovine Lf, a six residue sequence lying in an 18-loop region of the lactoferricin domain is key to Lf-LPS binding. There is much evidence that, by its action on LPS, Lf destabilizes the bacterial membrane and therefore increases bacterial permeability. By itself, Lf is not an effective antibacterial agent, but it permits the penetration of the bacterial membrane by some antibacterial substances whose hydrophobicity otherwise limits their efficacy. Additionally, Lf neutralizes free LPS by keeping the latter from forming complexes that activate TLR-4 signaling pathways. Such pathways, when over-activated, lead to the abundant production of pro-inflammatory mediators such as tumor necrosis factor (TNF) with fatal consequences to the host. The effect of Lf in reducing inflammation and destabilizing Gram negative bacteria has clinical implications in the control of sepsis, multiple organ dysfunction and bacterial invasion.
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Calzada del Hueso No. 1100, CP 04960, México DF Mexico. dragome@yahoo.com
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Drago-Serrano
authors.forename: Mireya
authors.initials: M
authors.lastname: de la Garza-Amaya
authors.forename: Jesús Serrano
authors.initials: JS
authors.lastname: Luna
authors.forename: Rafael
authors.initials: R
authors.lastname: Campos-Rodríguez
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007781:Lactoferrin / Q000737:chemistry / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D038042:Myelopoiesis / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D007781:Lactoferrin