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Lactoferrin (LF)

Lactoferrin (LF) is an iron-binding glycoprotein found in milk and other secretions and body fluids. LF is a member of the transferrin family and is involved in iron binding and delivery in mammals. Lactoferrin is a single-chain metal binding glycoprotein. Many cell types, such as monocytes, macrophages, lymphocytes, and brush-border cells in the intestine, are known to have lactoferrin receptors. Lactoferrin is found mainly in external secretions of mucosal epithelia such as breast milk, saliva, tears, bile, and pancreatic fluid and has a wide array of functions related to host primary defense mechanisms. A primary function of lactoferrin is to bind iron at the molecular level and thereby act as a highly effective antimicrobial agent. Iron is an essential growth factor for virtually every cell and microorganism, and free iron promotes the growth of pathogens in the intestines (bacteria, viruses and fungi), permitting invasion of the rest of the body through the intestinal walls. Lactoferrin is released by cells to absorb free iron that would otherwise be available to bacteria, viruses and fungi for growth. Unlike synthetic antibiotics, to which bacteria may develop resistance through mutation, lactoferrin exerts its bacteriostatic effect as long as the bacteria require iron for growth. This iron-binding protein is responsible for a wide range of nutraceutical benefits and provides protection against several intestinal illnesses. Lactoferrin plays an important role in various physiological pathways including inflammation by promoting neutrophil aggregation, inhibition of antibody-mediated cytotoxicity, specific growth stimulation of lymphocytes, down-regulation of myelopoiesis, complement cascade modulation by C3 convertase inhibition, intestinal iron absorption, enterocyte proliferation and gut maturation, up-regulation of thymocyte maturation, up-regulation of monocyte cytotoxicity, regulation of antibody production, regulation of cytokine production, down-regulation of tumor necrosis factor (TNF) and prevention of hydroxyradical-mediated tissue injury. Human milk is high in lactoferrin content. Human lactoferrin (hLF) is also a major component of the non-specific defense of mucosal surfaces and neutrophils and is active against a variety of pathogens. This protein displays antimicrobial properties against Gram-positive and Gram-negative bacteria by limiting the availability of environmental iron. Human lactoferrin is included in milk of human with high concentration. As a glycoprotein bound with iron, human lactoferrin has 80-kDa molecular weight and consists of two lobes. Each lobe has one iron-binding site. Lactoferrin is a multifunctional protein that is expressed in a variety of cell types under different mechanisms of control. It has been demonstrated that lactoferrin plays a central role in the inflammatory defense processes. Released in abundant quantities by neutrophils attracted to the site of an invasion, lactoferrin binds the iron made available by serum and damaged erythrocytes. Lactoferrin has many beneficial physiological activities and is related to various cellular defense mechanisms such as bacteriocidal and bacteriostatic action, regulation of cell proliferation, suppression of peroxy-lipid formation, regulation of immune system, regulation of iron-absorption, suppression of inflammation in infected area, anti-virus activity, prevention of E.coli from attaching to intestine cells, proliferation of Lactobacillus, etc. Lactoferrin also plays an important role in cell-mediated host immunity. It is present in high concentrations in all bodily secretions, such as tears, sweat, and ciliated respiratory mucous. Because it sequesters iron, lactoferrin can neutralize pathogenic microorganisms by preventing them from obtaining necessary iron at the site of entry, thereby preventing the spread of infection. Lactoferrin plays an important role in numerous inflammatory and immune response functions such as regulation of monocyte colony stimulating factor synthesis, activation of natural killer cell activity, inhibition of metastasis, and maturation of T-cells. Lactoferrin also inhibits myelopoiesis, binds to members of the low density lipoprotein receptor family, and blocks the clearance of lipoprotein chylomicron remnant particles.

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