Lactoferrin (LF) is a non-haem iron-binding protein that is part
of the transferrin protein family, along with serum transferrin,
ovotransferrin, melanotransferrin and the inhibitor of carbonic
anhydrase [1], whose function is to transport iron in blood serum.
[...]
This glycoprotein is found in mucosal secretions,
including tears, saliva, vaginal fluids, semen [3], nasal and bronchial
secretions, bile, gastrointestinal fluids, urine [4] and most highly in
milk and colostrum (7 g/L) [5], making it the second most abundant
protein in milk [6], after caseins. It can also be found in bodily
fluids such as blood plasma and amniotic fluid. LF is also found in
considerable amounts in secondary neutrophil granules (15g/106
neutrophils) [7], where it plays a significant physiological role. LF
possesses a greater iron-binding affinity and is the only transferrin
with the ability to retain this metal over a wide pH range [8],
including extremely acidic pH. It also exhibits a greater resistance to
proteolysis. In addition to these differences, LF’s net positive charge
and its distribution in various tissues make it a multifunctional
protein. It is involved in several physiological functions, including:
regulation of iron absorption in the bowel; immune response;
antioxidant, anticarcinogenic and anti-inflammatory properties;
and protection againstmicrobial infection, whichis themost widely
studied function to date. The antimicrobial activity of LF is mostly
due to two mechanisms. The first is iron sequestration in sites
of infection, which deprives the microorganism of this nutrient,
thus creating a bacteriostatic effect. The other mechanism is the
direct interaction of the LF molecule with the infectious agent.
The positive amino acids in LF can interact with anionic molecules
on some bacterial, viral, fungal and parasite surfaces, causing cell
lysis.
Considering the physiological capabilities of LF in host defence,
in addition to current pharmaceutical and nutritional needs, LF is
considered to be a nutraceutical and for several decades investigators
have searched for the most convenient way to produce it.
Today, we can obtain it as native LF isolated mostly from the milk
and colostrum of several mammals, or as recombinant LF (rLF)
generated from bacterial, fungal and viral expression systems. The
expression of this protein has also been attained in higher organisms
such as plants and mammals.[...]
Antiviral activity
LF possesses antiviral activity against a broad range of RNA and
DNA viruses that infect humans and animals [3].
Human respiratory syncytial virus is inhibited by LF at concentrations
ten times lower than those found in human milk. LF
also acts against non-enveloped viruses such as adenoviruses and
enteroviruses [35].
Human immunodeficiency virus (HIV) remains amajor medical
challenge, since current treatment of the syndrome that it causes is
not completely effective. In vitro studies show that, among human
plasma and milk proteins, LF exerts a strong activity against HIV.
This effect is due to inhibition of viral replication in the host cell
[36].
The antiviral mechanisms of LF have not yet been characterised.
LF can block the internalisation of certain viruses into the host cell,
such as poliovirus type 1 which causes poliomyelitis in humans
[37], herpes simplex virus types I and II [38] and cytomegalovirus
[39]. For other viruses, such as hepatitis C virus (HCV) [40] and
rotavirus [41], rather than preventing entry LF inhibits viral replication
in the host cell.
Several mechanisms of action have been proposed for LF’s
antiviral effects (Fig. 3). One of the most widely accepted hypotheses
is that LF binds to and blocks glycosaminoglycan viral receptors,
especially heparan sulfate (HS). The binding of LF and HS prevents
the first contact between virus and host cell and therefore prevents
the infection [3].
The antiviral effect of LF has also been observed in viruses that
infect animals, such as the Friend virus complex, which causes erythroleukaemia
in rodents [42], the feline calicivirus [43] and feline
immunodeficiency virus [44].[...]
