Lactoferrin in milk

Lactoferrin is the major whey protein present in breast milk (Teraguchi et ah, 1996) with many microbicidal properties (Leon-Sicairos et ah, 2006). The concentration of lactoferrin in milk has been reported as 1 g/liter in mature milk and 7 g/liter in colostrum (Houghton et ah, 1985). The concentration of lactoferrin in breast milk is controlled by the reproductive hormones prolactin and estrogen (Ward et ah, 2005). Lactoferrin has been demonstrated to resist digestion in the infant gut as it has been recovered intact from the stool of breast-fed infants (Bemt and Walker, 1999). Lactoferrin acts mainly in an iron-free state (apo-lactoferrin) and its microbicidal activity is reported to increase in proportion to its concentration in milk (Leon-Sicairos et ah, 2006). 

Masson, P. L. and Heremans, J. R. 1971. Lactoferrin in milk from different species. Comp. Biochem. Physiol. 39B, 119-129. 

The transferrins are a class of iron-binding glycoproteins which have been found in the blood serum of a variety of vertebrates and are presumably also present in moth hemolymph [see (74) and references therein], These proteins would appear to mediate the absorption and distribution of iron (75), and could play some role in the movement of carbon dioxide in the body (76). Proteins of similar characteristics, lactoferrin and conalbumin, have been isolated from milk and avian egg white respectively. It has been proposed (77) that conalbumin could prevent bacterial contamination of the egg yolk by removing free iron. A similar bacteriostatic action could be performed by lactoferrin in milk, and it is possible that this protein is involved in controlling the intestinal flora in infants (78). 

Van Berkel, P.H., Welling, M.M., Geerts, M. et al. (2002) Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nature Biotechnology, 20 (5), 484—487. 

Research is under way to investigate the potential to develop the natural antimicrobial system present in milk, such as the lysozyme, lactoferrin,... 

So called because they are found in milk, where the iron-binding protein lactoferrin sequesters iron so tightly... 

Senft, B. and Klobasa, F. 1973. Research on the concentration of lactoferrin in colostral and ripe milk from cows. Milchwissenschaft 28, 750-752 (German). 

The transferrins are proteins that bind and transport iron as peIII 16-U.8 They indude lactoferrin from milk, ovotransferrin from egg white, and serum transferrin from a range of organisms. Uteroferrin, considered in Section 62.1.5.5.2 on the purple acid phosphatases, is an iron-binding protein with phosphatase activity, that has been proposed to transport iron from maternal to foetal circulation.824 826 There are distinct differences between the iron-binding sites in uteroferrin and transferrin, and so uteroferrin will not be discussed in this section. 

Human lactoferrin (HL) is a component of innate immunity. Human lactoferrin is an iron-binding protein found in milk, granulocytes and exocrine secretions. It is released during inflammation, has bactericidal effects and reduces cytokine production by binding to the lipid A portion of endotoxin (Appelmelk et al., 1994). 

Hambraeus, L. and Lonnerdal, B. 1994. The physiological role of lactoferrin. In Indigenous Antimicrobial Agents of Milk—Recent Developments , IDF Special Issue 9404, pp. 97-107. 

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. 

Distribution of Cu in milk has been studied by SEC coupled to ICP-AES [12, 14], and ICP-MS [15, 17-19], or even using electrothermal atomization atomic emission spectrometry (ET-AAS) for the detection [20]. Breast milk Cu seems to be distributed all over the biocompounds from high (caseins, immunoglobulins, lactoferrin, and serum albumin) to lower-molecular-weight ligands (lac-toalbumin, peptones, free aminoacids, citrates, etc.). The distribution patterns of Cu have been shown to be very different in mature milk and colostrum [18] (Fig. 17.3). 

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. 

Because most of the first transition series elements are essential in biological systems there is considerable interest in the possibility that transferrins may be involved in their binding and translocation. This is certainly a distinct possibility, because neither transferrin nor lactoferrin is more than 30% saturated with iron in body fluids. There is as yet little hard evidence, however. Transferrin has been reported to be the main carrier for manganese in blood (158), just as lactoferrin is in milk (25), and thermodynamic studies suggest that transferrin is also capable of competing with serum albumin for zinc under the... 

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). 

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. 

---