Ricerc@Sapienza

Human and bovine lactoferrin (hLf and
bLf) are multifunctional iron-binding glycoprotein
constitutively synthesized and secreted by glandular
epithelial cells and by neutrophils following induction.
HLf and bLf possess very high similarity of sequence.
Therefore, most of the in vitro and in vivo studies are
carried out with commercial bLf (cbLf), available in
large quantities and recognized by Food and Drug
Administration (FDA, USA) as a safe substance.
Physico-chemical heterogeneity of different cbLf
preparations influences their effectiveness. CbLf
iron-saturation affects thermal stability and resistance
to proteolysis. Moreover, other metal ions such as
Al(III), Cu(II), Mg(II), Mn(II), Zn(II) are chelated by
cbLf, even if at lower affinity than Fe(III). Ca(II) is
also sequestered by the carboxylate groups of sialic
acid present on glycan chains of cbLf thus provoking
the release of LPS, contributing to bactericidal activity. Similarly to more than 50% of eukaryotic proteins,
cbLf possesses five N-glycosylation sites, also contributing to the resistance to proteolysis and, putatively, to the protection of intestinal mucosa from
pathogens. CbLfs possess several functions as antimicrobial, anti-biofilm, anti-adhesive, anti-invasive
and anti-inflammatory activities. They are also relevant modulators of iron and inflammatory homeostasis. However, the efficacy of cbLfs in exerting several
functions can be erratic mainly depending from
integrity, degree of iron and other metal ions saturation, N-glycosylation sites and chains, desialylated
forms, Ca(II) sequestration, presence of contaminants
and finally the ability to enter inside nucleus.