Lactoferrin (LF), also known as lactotransferrin (LTF), is a globular multifunctional protein with antimicrobial activity (bacteriocide, fungicide) and is part of the innate defense, mainly at mucoses. Lactoferrin is found in milk and many mucosal secretions such as tears and saliva. Lactoferrin is also present in secondary granules of PMN and also is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum has the highest concentration, followed by human milk, then cow milk. Lactoferrin belongs to the transferrin family proteins (TF, melanotransferrin, ovotransferin, etc.). Its molecular mass is 80,000 u (80 kDa). It generally contains two bound Fe+2 ions. It contains 4 identical domains, with two surrounding each iron atom.
Lactoferrin antimicrobial activity is due partly to its high affinity for Fe (ferric state). LF proteolysis produces lactoferricin, kaliocin-1 small peptides with antimicrobial activity. The combination of iron and lactoferrin in mucosal secretions modulate the ability and aggregation of pathogenic bacteria, and inhibit both bacteria and viruses by binding to host cells/viral particles. This inhibits the ability of bacteria and viruses to attach to cell membranes. It is also an antifungal agent. Lactoferrin receptors have been found on brush-border cells, PMN, monocytes, Mφ and activated lymphocytes. Lactoferrin inhibits dendritic cell-mediated HIV-1 transmission by blocking gp120 to DC-SIGN , which is a critical protein that never changes regardless of strain.
A minor fraction of whey, lactofer-rin appears to have a wide variety of uses in biological systems and is considered a first line immune defense in the human body. Though a natural component of cows’ and human mothers’ milk, lactoferrin is found through-out the human body. Published studies that have examined the use of lactoferrin as a supplement and its beneficial effects on immunity have been quite promising. Lactoferrin helps to maintain a proper level of “good” bacteria in the intestinal tract, while controlling the number of “bad” bacteria. Probably lactoferrin’s best-known role is as an iron binding protein. The mechanism appears to lie with lactoferrin’s ability to bind iron, as it is known to have an extremely high affinity for this metal. Lactoferrin is a non-heme iron binding glycoprotein produced during lactation and by epithelial cells at mucosal surfaces. The protein is a prominent component of the first line of mammalian host defense and its expression is upregulated in response to inflammatory stimuli. In this paper, the antibacterial and immune modulatory properties of lactoferrin that contribute to host defense are reviewed.