Lactoferrin proteins

Masson, P. (1970) La Lactoferrine, Proteine des Secretions Externes et des Leucocytes Neutrophiles. Arscia, Bruxelles. 

Aguas, A., Esaguy, N., Sunkel, C.E., Silva, M.T. (1990). Cross-reactivity and sequence homology between the 65 kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect. Immun. 58, 1461-1470. 

Lactoferrin j Iron-binding protein May inhibit growth of certain bacteria by binding iron and may be involved in regulation of proliferation of myeloid cells... 

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

In a similar fashion, polyethylene glycol can be activated with CDI for connection to a protein, as has been shown for superoxide dismutase, a2-macroglobulin, a2-macro-globulin-trypsin, lactoferrin, and tissue plasminogen activator t208] [209]... 

Iron transport agents may belong to the protein or non-protein class. In the former group are found the animal proteins transferrin (25), lactoferrin (26) and conalbumin (27). The low molecular weight iron carrying compounds from microorganisms, the siderochromes, may occur with or without a bound metal ion. Typically, severe repression of biosynthesis of these substances can be expected to set in at an iron concentration of ca. 2 x 10-5 g atoms/liter (28). Most, but not all, of these substances can be described as phenolates or hydroxamates (4). 

Fig. 9. Comparison of FTIR absorption spectra of four proteins in H20 (left, amide I + II) and D20 (right, amide F + IF). Comparison between protein spectra for dominant secondary structure contributions from a-helix (myoglobin, MYO, top), /Fsheet (immunoglobin, IMUN), from both helix and sheet (lactoferrin, LCF) and from no long-range order (o -casein, CAS, bottom). The comparisons emphasize the high similarity, differing mostly by small frequency shifts of the amide I with the changes in secondary structure.

Figures 9 and 10 represent a selected comparison of amide V and I+II FTIR and VCD for four proteins in D2O solution. Of these, myoglobin (MYO) has a very high fraction of a-helix, immunoglobulin (IMU) has substantial /1-sheet component, lactoferrin (LAF) has both a and j3 contributions, and a-casein (CAS) supposedly has no extended structure. The FTIR spectra of these proteins change little, the primary difference...

Transferrin iron uptake via receptor-mediated endocytosis has clearly appeared fairly late in evolution, when we consider that the bilobal iron-binding protein is found only as far back as insects . As we have seen in the preceding chapters, iron-uptake mechanisms involving the synthesis of more or less specific siderophores have evolved together with strategies implying the solubilization of insoluble ferric iron by the combined effects of pH and reduction, and even the development of receptor proteins capable of taking up transferrin-, lactoferrin- or haem-bound iron from specific hosts. 

Beauchamp, C.O., Gonias, S.L., Menapace, D.P., and Pizzo, S.V. (1983) A new procedure for the synthesis of polyethylene glycol-protein adducts Effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and a2macroglobulin. Anal. Biochem. 131, 25-33. 

Lactoferrin, a protein found in secondary granules of polymorphonuclear cells, was observed to be mildly to moderately elevated in the stools of children with endemic cryptosporidiosis [91] and healthy adult volunteers with experimental infection [92], Indeed, in another study of malnourished children in Haiti, cryptosporidiosis was noted to stimulate an inflammatory response, as evidenced by elevated IL-8, TNF-a, lactoferrin, IL-13 and IL-10 [93]. Further studies are needed to elucidate the role of inflammatory mediators in the development of prolonged diarrhea, malabsorption and malnutrition in immunocompromised hosts and children in endemic areas. 

The Gram-positive bacterium Streptococcus pneumoniae is an important cause of respiratory tract infections, bacteremia, and meningitis. In this strain, the cell wall anchored pneumococcal surface protein A (PspA) has been demonstrated to bind lactoferrin [181]. PspA and closely related proteins in a variety of pneumococcal isolates are most likely involved in the sequestration of iron from lactoferrins, and finally contribute to the virulence of these bacteria. However, the means by which the pneumococcus acquires iron at the mucosal surface during invasive infection is not well understood at the molecular level [182],... 

Hammerschmidt, S., Bethe, G., Remane, P. H. and Chhatwal, G. S. (1999). Identification of pneumococcal surface protein A as a lactoferrin-binding protein of Streptococcus pneumoniae, Infect. Immun., 67, 1683-1687. 

Hakansson, A., Roche, H., Mirza, S., McDaniel, L. S., Brooks-Walter, A. and Briles, D. E. (2001). Characterization of binding of human lactoferrin to pneumococcal surface protein A, Infect. Immun., 69, 3372-3381. 

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

The peroxidase-negative granules produced later in neutrophil development are termed secondary or specific granules (because they stain only with specific dyes). They are twice as abundant in the cytoplasm of the mature neutrophil as the azurophilic granules. Specific granules contain much of the lysozyme, lactoferrin, vitamin-B 12-binding protein, adhesin receptors, fMet-Leu-Phe receptors, and cytochrome b.245. 

---