Lactoferrin human milk

NHH Heegaard, J Brimnes. Comparison of heparin binding to lactoferrin from human milk and from human granulocytes by means of affinity capillary electrophoresis. Electrophoresis 17 1916-1920, 1996. 

Lactoferrin occurs in high concentrations in human milk. It has high affinity for iron, and it may have a bacteriostatic function in depriving microbes of essential iron required for their growth. It supplies iron to intestinal tissue and probably has a nutritional role in supplying iron to newly born infants. 

It is interesting to note that /3-lactoglobulin is the major protein in cow s milk whey, but it is absent from human milk whey. However, the content of a-lactoalbumin and immunoglobulins (Ig) is higher in human than in cow s milk whey. Serum albumin and lactoferrins are found in similar concentrations in human and cow s milk whey, and the amount of lactoferrin is higher in colostrum than in mature milk. In any case, lactoferrin is present in milk throughout the lactation period. 

G. Harzer, J. G. Bindels, Changes in human milk immunoglobulin A and lactoferrin during early lactation, in J. Schaub (ed.), Composition and Physiological Properties of Human Milk, Elsevier Science, Amsterdam, 1985, pp. 285-295. 

We subsequently used extrinsically labeled diets for further fractionation by gel filtration and immunoaffinity chromatography. Mn in human milk was found to be predominantly (about 70%) bound to lactoferrin, the major iron-binding protein in human milk. Minor amounts were bound to casein in human milk and the milk fat globule membrane. It is therefore possible that changes in lactoferrin concentration in human milk may explain the developmental pattern... 

A further important constituent of human milk, which is not present in formula milk, is lactoferrin, which complexes iron in milk so reducing the iron available for gram-negative bacteria to multiply in the infant gut. 

The recombinant whole molecules are both expressed in glycosylated form, although the glycosylation patterns differ from the proteins isolated from natural sources. The recombinant human transferrin binds to receptors both in its glycosylated form and as a nonglycosylated mutant, showing that the carbohydrate is not required for receptor binding (230). Recombinant human lactoferrin shows identical spectroscopic properties and shows an identical profile of pH-dependent iron release when compared with human milk lactoferrin (231). 

Lactoferrin was first identified as a red protein fraction in human milk (1). The milk protein has been called by various names of red milk protein, ekkrino-siderophilin, and lactotransferrin which is in turn very similar in many respects to transferrin, the ironbinding protein of serum. The concentration of lactoferrin in human milk is unusally rich with a range of 7 mg/ml in colostrum to approximately 1 mg/ml in mature milk (2). However, the bovine colostrum contains lactoferrin at concentrations of 5 mg/ml, which drops very rapidly with stage of lactation to where mature bovine milk contains 20-200 pg/ml of lactroferrin (3). Lactoferrin is also found in various other exocrine secretions of the body such as vaginal, nasal, bronchial and intestinal (4 6). 

Lactoferrin s role in iron absorption was demonstrated by the addition of lactoferrin, presumably iron-saturated, to a lactoferrin free simulated human milk. Administered to adults it did not increase iron absorption (13). The addition of apolactoferrin was shown to actually inhibit iron uptake by rat and guinea-pig in everted duodenal sacs, while the addition of Fe 2- lactoferrin had no effect on uptake of iron (14). An additional study demonstrated a negative relationship between duodenal lactoferrin concentration and iron absorption in adults (15). These results would suggest that lactoferrin has no role or even a negative role in iron absorption. Further, additional studies brings into question the role, if any at all, that lactoferrin has in iron absorption. McMillan et al. (13) have shown that the iron in human milk, despite the high lactoferrin content, is more readily absorbed than iron from a simulated human milk of comparable iron content. The... 

The analysis of human milk for the distribution of iron into the various components found iron in three fractions of lipid, low molecular weight form and lactoferrin (16). The total concentration of milk iron varied from 0.26 to 0.73 mg/ml with 15 to 46% of the iron bound to the lipid fraction, and 18 to 50% found in a low molecular weight fraction. Surprisingly, only a small amount of iron was bound to the lactoferrin, which was saturated at 1-4%. These results even further complicate the role of lactoferrin in iron absorption by infants. Further experimental work needs to be done to define the role of lactoferrin in iron absorption, if any at all. 

With the exact role of lactoferrin uncertain and the mechanism of iron absorption also unknown, the concentration of iron and other trace elements in human milk is a controversal item. The data involving iron levels in breast milk date from the early fifties to the present time. During the stage of lactation, colostrum, early and mature milk samples are known to decrease in iron concentration with time, see Table II (17,18). The comparison of mature breast milk, 7 days or older, finds a range in iron concentration from 0.21 to 1.28 mg/liter. Weekly, daily and diurinal variation within a given day were demonstrated for iron, copper and zinc in human milk samples (20). Great variations were found within a given day on total yield, fat, and mineral levels (17,20). 

Researchers (Nuijens et al., 1997) at the Leiden University (the Netherlands) in collaboration with Pharming, NV (Leiden, the Netherlands) compared recombinant human lactoferrin (rhLF) expressed in the milk of transgenic mice with natural human milk-derived lactoferrin (hLF). They concluded that the unsaturated rhLF and natural hLF had comparable properties, indicating that hLF produced in bovine milk will exert similar, if not identical, antibacterial and anti-inflammatory activities in vivo. Pharming also developed the first transgenic bull in the late... 

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