title: 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 10(9) 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.
authors.affiliation: Department of Medical Microbiology, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Appelmelk
authors.forename: Y Q
authors.initials: YQ
authors.lastname: An
authors.forename: M
authors.initials: M
authors.lastname: Geerts
authors.forename: B G
authors.initials: BG
authors.lastname: Thijs
authors.forename: H A
authors.initials: HA
authors.lastname: de Boer
authors.forename: D M
authors.initials: DM
authors.lastname: MacLaren
authors.forename: J
authors.initials: J
authors.lastname: de Graaff
authors.forename: J H
authors.initials: JH
authors.lastname: Nuijens
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D008050:Lipid A / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D013400:Sugar Acids / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate; D007781:Lactoferrin