Lactoferrin is a lipid A-binding protein

Abstract

Lactoferrin (LF), a cationic 80-kDa protein present in polymorphonuclear leukocytes and in mucosal secretions, is known to have antibacterial effects on gram-negative bacteria, with a concomitant release of lipopolysaccharides (LPS, endotoxin). In addition, LF is known to decrease LPS-induced cytokine release by monocytes and LPS priming of polymorphonuclear leukocytes. Its mechanism of action is incompletely understood. We have now demonstrated by in vitro-binding studies that LF binds directly to isolated lipid A and intact LPS of clinically relevant serotypes of the species which most frequently cause bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), as well as to lipid A and LPS of mucosal pathogens (among others, Neisseria meningitides and Haemophilus influenzae). Binding to LPS was inhibitable by lipid A and polymyxin B but not by KDO (3-deoxy-D-manno-octulosonate), a glycoside residue present in the inner core of LPS. Binding of LF to lipid A was saturable, and an affinity constant of 2 x 109 M-1 was calculated for the LF-lipid A interaction. Our data may explain, in part, the mechanism whereby LF exerts its antibacterial and anti-endotoxic effects. Further studies on the ability of LF to block the detrimental effects of LPS, both in vitro and in vivo, are warranted.

Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens

“…The transport of haem and haem-derived iron in P. gingivalis involves both high and low a¤nity receptors. The high a¤nity, receptor is thought to be a speci¢c binding protein for the protoporphyrin IX ring [21], while the low a¤nity binding sites are unlikely to be speci¢c receptors [22] and include lipopolysaccharides (LPS) [23]. Here we have shown that apoLf reduced haemin uptake by all three species and caused release of cell-bound haemin, both of which support the possibility that the growth inhibitory e¡ect of Lf is due to depriving cells of haemin.…”

Bovine whey proteins – Overview on their main biological properties

“…coliforms), because apo-BLF was also shown to possess bactericidal power against a wide range of microorganisms (Dionysius, Grieve, & Milne, 1993). BLF can damage the outer membrane of Gram-negative bacteria via binding to Lipid A lipopolysaccharides (LPS)which compose their asymmetric lipid bilayer membrane (Appelmelk et al, 1994); release thereof causes structural changes, which include loss of membrane potential and integrity. The antibacterial activity of LF also depends on its concentration or the degree of iron saturation of the molecule, and on its interaction with mineral medium constituents (Payne, Davidson, Oliver, & Christen, 1990).…”

The efficacy of bovine lactoferrin in the treatment of cows with experimentally inducedEscherichia colimastitis

“…In addition, specific portions of Lf molecules are directly toxic to microbes. Lactoferrin increases bacterial cell membrane permeability and directly damages the outer membrane of Gramnegative bacteria (Ellison et al, 1988;Yamauchi et al, 1993;Appelmelk et al, 1994) by binding to lipopolysaccharide (LPS) and blocking its detrimental effects (Appelmelk et al, 1994).…”