Biological role of lactoferrin.

Abstract

Lactoferrin is an iron-binding protein closely related in structure to the serum iron transport protein transferrin. Unlike transferrin, only traces are normally present in serum, and it is instead found mainly in milk and other external secretions, and in the secondary granules of neutrophils. Although lactoferrin was first isolated 30 years ago, its biological role remains unclear. Some aspects of its function were discussed about 12 years ago in this journal,' and this review will attempt to reassess the function of lactoferrin in the light of the large amount of new information that has accrued since then. Knowledge of the structure of lactoferrin has been advanced by recent x ray crystallographic studies, and the structure and iron binding properties of lactoferrin are reviewed in detail elsewhere.2 Briefly lactoferrin, like transferrin, reversibly binds two ferric ions, for which synergistic binding of an anion, usually bicarbonate or carbonate, is necessary. However, its affinity constant for iron is 300 times greater than that of transferrin, and even in the presence of a competing iron chelator such as citrate it can retain iron down to pH 3 or less while transferrin loses it at pH 5. Unlike transferrin, lactoferrin is strongly basic. Human lactoferrin has been cloned and sequenced4 and the recombinant protein expressed in baby hamster kidney cells.5 bearing in mind when considering its possible biological function. Human milk contains 3-6-12-5 ,umol/l of iron, and of this only 60-70% is in the whey fraction, the remainder being in the lipid fraction (11-20%) or bound to casein (2-14%). As a consequence, milk lactoferrin is only 6-8% saturated with iron, presumably because of the difficulty in gaining access to iron in the lipid fraction or casein micelles.