Genetic constructs containing the human lactoferrin (hLf) gene were created within a joint program of Russian and Belorussian scientists. Using these constructs, transgenic mice were bred (the maximum hLf concentration in their milk was 160 g/L), and transgenic goats were also generated (up to 10 g/L hLf in their milk). Experimental goatherds that produced hLf in their milk were also bred, and the recombinant hLf was found to be identical to the natural protein in its physical and chemical properties. These properties included electrophoretic mobility, isoelectric point, recognition by polyclonal and monoclonal antibodies, circular dichroic spectra, interaction with natural ligands (DNA, lipopolysaccharides, and heparin), the binding of iron ions, the sequence of the 7 terminal amino acids, and its biological activity. The latter was assessed by the agglutination of Micrococcus luteus protoplasts, bactericidal activity against Escherichia coli and Listeria monocytogenes , and fungicidal activity against Candida albicans . We also demonstrated a significant increase in the activity of antibiotics when used in combination with Lf.
The effect of the innovative product Neolactoferrin, a natural combination of
recombinant human lactoferrin (90%) and goat lactoferrin (10%) isolated from
the milk of transgenic goats carrying the full-length human lactoferrin gene,
on human immune system cells was studied. Neolactoferrin enhanced the
production of IL-1β. Neolactoferrin saturated with iron ions increased the
synthesis of pro-inflammatory cytokine TNFα. It determined the direction
of the differentiation of precursor dendrite cells. Under the action of T
cells, Neolactoferrin amplified the expression of the transcription factors
responsible for the differentiation of Th- and Treg-cells and stimulated the
production of both IFNγ and IL-4. The results suggest that Neolactoferrin
exhibits an immunotropic activity and hinders the development of immune
inflammatory processes. Iron saturation of Neolactoferrin increases its
pro-inflammatory activity.
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