Editing Lactoferrin

{{short description|Mammalian protein found in Homo sapiens}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox_gene}}
'''Lactoferrin''' ('''LF'''), also known as '''lactotransferrin''' ('''LTF'''), is a multifunctional [[protein]] of the [[transferrin]] family. Lactoferrin is a [[globular proteins|globular]] [[glycoprotein]] with a molecular mass of about 80 [[Atomic mass unit|kDa]] that is widely represented in various secretory fluids, such as [[milk]], [[saliva]], [[tears]], and [[Mucus|nasal secretions]]. Lactoferrin is also present in secondary granules of [[Granulocyte|PMNs]] and is secreted by some [[Centroacinar cells|acinar cells]]. Lactoferrin can be purified from milk or produced [[Recombinant DNA|recombinantly]]. Human [[colostrum]] (''"first milk"'') has the highest concentration, followed by human milk, then cow milk (150&nbsp;mg/L).<ref name="pmid1599309" />

Lactoferrin is one of the components of the [[immune system]] of the body; it has antimicrobial activity ([[bacteriocide]], [[fungicide]]) and is part of the innate defense, mainly at mucoses.<ref name="pmid1599309">{{Cite journal |vauthors=Sánchez L, Calvo M, Brock JH |date=May 1992 |title=Biological role of lactoferrin |journal=Archives of Disease in Childhood |volume=67 |issue=5 |pages=657–61 |doi=10.1136/adc.67.5.657 |pmc=1793702 |pmid=1599309}}</ref> It is constantly produced and released into saliva, tears, as well as seminal and vaginal fluid.<ref name="pmid36874560">{{cite journal | vauthors=Ashraf MF, Zubair D, Arain MA | title=Nutraceutical and Health-Promoting Potential of Lactoferrin, an Iron-Binding Protein in Human and Animal: Current Knowledge | journal=[[Biological Trace Element Research]] | pages=56–72 | year=2023 | volume=202 | issue=1 | doi = 10.1007/s12011-023-03658-4 | pmc=10104436 | pmid=37059920}}</ref> Lactoferrin provides [[Antiseptic|antibacterial]] activity to human infants.<ref name="isbn 0-8247-5329-1">{{Cite book |url=https://books.google.com/books?id=E3bvD2jU4B0C&pg=PA1028 |title=Food biotechnology |vauthors=Levin RE, Kalidas S, Gopinadhan P, Pometto A |publisher=CRC/Taylor & Francis |year=2006 |isbn=978-0-8247-5329-0 |location=Boca Raton, FL |page=1028}}</ref><ref name="isbn 90-5702-292-3">{{Cite book |title=Animal Breeding: Technology for the 21st Century (Modern Genetics) |vauthors=Pursel VG |publisher=CRC |year=1998 |isbn=978-90-5702-292-0 |veditors=Clark AJ |location=Boca Raton |page=191 |chapter=Modification of Production Traits |chapter-url=https://books.google.com/books?id=Ts41TBTi9QMC&pg=PA191}}</ref> Lactoferrin  interacts with [[DNA]] and [[RNA]], [[polysaccharides]] and [[heparin]], and shows some of its biological functions in complexes with these [[Ligand (biochemistry)|ligand]]s. 

Lactoferrin supplements reduce the risk of respiratory tract infections, based on a recent meta-analysis of randomized controlled trials.<ref>{{cite journal | vauthors = Ali AS, Hasan SS, Kow CS, Merchant HA | title = Lactoferrin reduces the risk of respiratory tract infections: A meta-analysis of randomized controlled trials | journal = Clinical Nutrition ESPEN | volume = 45 | pages = 26–32 | date = October 2021 | pmid = 34620326 | doi = 10.1016/j.clnesp.2021.08.019 | s2cid = 238475090 | url = https://pure.hud.ac.uk/ws/files/39527111/Lf_Manuscript_v12.0_Authors_version.pdf }}</ref> As with any supplements sold online, quality may be an issue because nutritional supplement production quality controls are not subject to the same strict regulatory process as medicines.<ref>{{Cite web|title=Lactoferrin supplements could aid in the recovery of COVID19 & other Respiratory Tract Infections|url=https://www.eurekalert.org/news-releases/932115|access-date=2022-02-18|website=EurekAlert!|language=en}}</ref>

==History==
Occurrence of iron-containing red protein in bovine milk was reported as early as in 1939;<ref>M. Sorensen and S. P. L. Sorensen, Compf. rend. trav. lab. Carlsberg (1939) 23, 55, cited by Groves (1960)</ref> however, the protein could not be properly characterized because it could not be extracted with sufficient purity. Its first detailed studies were reported around 1960. They documented the molecular weight, [[isoelectric point]], optical absorption spectra and presence of two iron atoms per protein molecule.<ref>{{Cite journal | vauthors = Groves ML |year=1960 |title=The Isolation of a Red Protein from Milk |journal=Journal of the American Chemical Society |volume=82 |issue=13 |page=3345 |doi=10.1021/ja01498a029}}</ref><ref name=j60/> The protein was extracted from milk, contained iron and was structurally and chemically similar to [[Blood serum|serum]] [[transferrin]]. Therefore, it was named lactoferrin in 1961, though the name lactotransferrin was used in some earlier publications, and later studies demonstrated that the protein is not restricted to milk. The antibacterial action of lactoferrin was also documented in 1961, and was associated with its ability to bind iron.<ref name="isbn 0-8493-0909-3">{{Cite book |url=https://books.google.com/books?id=2oTsweiwImAC&pg=PA2 |title=Lactoferrin: natural, multifunctional, antimicrobial |vauthors=Naidu AS |publisher=CRC Press |year=2000 |isbn=978-0-8493-0909-0 |location=Boca Raton |pages=1–2}}</ref>

==Structure==

===Genes of lactoferrin===
At least 60 gene sequences of lactoferrin have been characterized in 11 species of mammals.<ref name="Jing">{{Cite journal |vauthors=Kang JF, Li XL, Zhou RY, Li LH, Feng FJ, Guo XL |date=June 2008 |title=Bioinformatics analysis of lactoferrin gene for several species |journal=Biochemical Genetics |volume=46 |issue=5–6 |pages=312–22 |doi=10.1007/s10528-008-9147-9 |pmid=18228129|s2cid=952135 }}</ref> In most species, [[stop codon]] is TAA, and TGA in ''[[Mus musculus]]''. Deletions, insertions and mutations of stop codons affect the coding part and its length varies between 2,055 and 2,190  [[nucleotide]] pairs. Gene polymorphism between species is much more diverse than the intraspecific polymorphism of lactoferrin. There are differences in amino acid sequences: 8 in ''[[Homo sapiens]]'', 6 in ''[[Mus musculus]]'', 6 in ''[[Capra hircus]]'', 10 in ''[[Bos taurus]]'' and 20 in ''[[Sus scrofa]]''. This variation may indicate functional differences between different types of lactoferrin.<ref Name=Jing />

In humans, lactoferrin gene ''LTF'' is located on the third [[chromosome]] in the [[locus (genetics)|locus]] 3q21-q23. In [[ox]]en, the coding sequence consists of 17 [[exon]]s and has a length of about 34,500  [[nucleotide]] pairs. Exons of the lactoferrin gene in oxen have a similar size to the exons of other genes of the [[transferrin]] family, whereas the sizes of introns differ within the family.  Similarity in the size of exons and their distribution in the domains of the protein molecule indicates that the evolutionary development of lactoferrin gene occurred by duplication.<ref>{{Cite journal |vauthors=Seyfert HM, Tuckoricz A, Interthal H, Koczan D, Hobom G |date=June 1994 |title=Structure of the bovine lactoferrin-encoding gene and its promoter |journal=Gene |volume=143 |issue=2 |pages=265–9 |doi=10.1016/0378-1119(94)90108-2 |pmid=8206385}}</ref> Study of polymorphism of genes that encode lactoferrin helps selecting livestock breeds that are resistant to [[mastitis]].<ref name="Biochimie_2009">{{Cite journal |vauthors=O'Halloran F, Bahar B, Buckley F, O'Sullivan O, Sweeney T, Giblin L |date=January 2009 |title=Characterisation of single nucleotide polymorphisms identified in the bovine lactoferrin gene sequences across a range of dairy cow breeds |journal=Biochimie |volume=91 |issue=1 |pages=68–75 |doi=10.1016/j.biochi.2008.05.011 |pmid=18554515}}</ref>

===Molecular structure===
Lactoferrin is one of the transferrin proteins that transfer [[iron]] to the cells and control the level of free iron in the blood and external secretions. It is present in the milk of humans and other mammals,<ref name="j60">{{Cite journal |vauthors=Johansson B, Virtanen AI, Tweit RC, Dodson RM |year=1960 |title=Isolation of an iron-containing red protein from human milk |url=http://actachemscand.org/pdf/acta_vol_14_p0510-0512.pdf |journal=Acta Chem. Scand. |volume=14 |issue=2 |pages=510–512 |doi=10.3891/acta.chem.scand.14-0510|doi-access=free }}</ref> in the [[blood plasma]] and [[neutrophil]]s and is one of the major proteins of virtually all exocrine secretions of mammals, such as [[saliva]], [[bile]], [[tears]] and [[pancreas]].<ref name="pmid3858982">{{Cite journal |vauthors=Birgens HS |date=April 1985 |title=Lactoferrin in plasma measured by an ELISA technique: evidence that plasma lactoferrin is an indicator of neutrophil turnover and bone marrow activity in acute leukaemia |journal=Scandinavian Journal of Haematology |volume=34 |issue=4 |pages=326–31 |doi=10.1111/j.1600-0609.1985.tb00757.x |pmid=3858982}}</ref> Concentration of lactoferrin in the milk varies from 7 g/L in the [[colostrum]] to 1 g/L in mature milk.{{cn|date=January 2024}}{{clarify|reason=Which species|date=January 2024}}

[[X-ray crystallography|X-ray diffraction]] reveals that lactoferrin is based on one [[polypeptide]] chain that contains about 700 amino acids and forms two homologous globular [[Protein domain|domains]] named N-and C-lobes. N-lobe corresponds to amino acid residues 1-333 and C-lobe to 345-692, and the ends of those domains are connected by a short α-helix.<ref name="isbn 0-444-50317-X">{{Cite book |title=Lactoferrin: structure, function, and applications: proceedings of the 4th International Conference on Lactoferrin: Structure, Function, and Applications, held in Sapporo, Japan, 18-22 May 1999 |url=https://archive.org/details/lactoferrinstruc0000inte |url-access=registration |vauthors=Baker HM, Anderson BF, Kidd RD, Shewry SC, Baker EN |publisher=Elsevier |year=2000 |isbn=978-0-444-50317-6 |veditors=Shimazaki K |location=Amsterdam |chapter=Lactoferrin three-dimensional structure: a framework for interpreting function}}</ref><ref name="pmid16261257">{{Cite journal |vauthors=Baker EN, Baker HM |date=November 2005 |title=Molecular structure, binding properties and dynamics of lactoferrin |journal=Cellular and Molecular Life Sciences |volume=62 |issue=22 |pages=2531–9 |doi=10.1007/s00018-005-5368-9 |pmid=16261257|s2cid=218464085 |pmc=11139133 }}</ref> Each lobe consists of two subdomains, N1, N2 and C1, C2, and contains one iron binding site and one [[glycosylation]] site. The degree of glycosylation of the protein may be different and therefore the molecular weight of lactoferrin varies between 76 and 80 kDa. The stability of lactoferrin has been associated with the high glycosylation degree.<ref name="pmid7644538">{{Cite journal |vauthors=Håkansson A, Zhivotovsky B, Orrenius S, Sabharwal H, Svanborg C |date=August 1995 |title=Apoptosis induced by a human milk protein |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=92 |issue=17 |pages=8064–8 |bibcode=1995PNAS...92.8064H |doi=10.1073/pnas.92.17.8064 |pmc=41287 |pmid=7644538|doi-access=free }}</ref>

Lactoferrin belongs to the basic proteins, its [[isoelectric point]] is 8.7. It exists in two forms: iron-rich hololactoferrin and iron-free apolactoferrin. Their tertiary structures are different; apolactoferrin is characterized by "open" conformation of the N-lobe and the "closed" conformation of the C-lobe, and both lobes are closed in the hololactoferrin.<ref name="pmid10089508">{{Cite journal |vauthors=Jameson GB, Anderson BF, Norris GE, Thomas DH, Baker EN |date=November 1998 |title=Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change |journal=Acta Crystallographica Section D |volume=54 |issue=Pt 6 Pt 2 |pages=1319–35 |doi=10.1107/S0907444998004417 |pmid=10089508|bibcode=1998AcCrD..54.1319J }}</ref>

Each lactoferrin molecule can reversibly bind two ions of iron, [[zinc]], [[copper]] or other metals.<ref name="pmid7672721">{{Cite journal |vauthors=Levay PF, Viljoen M |year=1995 |title=Lactoferrin: a general review |journal=Haematologica |volume=80 |issue=3 |pages=252–67 |pmid=7672721}}</ref> The binding sites are localized in each of the two protein globules. There, each ion is bonded with six ligands: four from the polypeptide chain (two [[tyrosine]] residues, one [[histidine]] residue and one [[aspartic acid]] residue) and two from [[carbonate]] or [[bicarbonate]] ions.

Lactoferrin forms a reddish complex with iron; its affinity for iron is 300 times higher than that of [[transferrin]].<ref name="pmid6770907">{{Cite journal |vauthors=Mazurier J, Spik G |date=May 1980 |title=Comparative study of the iron-binding properties of human transferrins. I. Complete and sequential iron saturation and desaturation of the lactotransferrin |journal=Biochimica et Biophysica Acta |volume=629 |issue=2 |pages=399–408 |doi=10.1016/0304-4165(80)90112-9 |pmid=6770907}}</ref> The affinity increases in weakly acidic medium. This facilitates the transfer of iron from transferrin to lactoferrin during [[inflammation]]s, when the pH of tissues decreases due to accumulation of [[lactic acid|lactic]] and other acids.<ref name="Sousa">{{Cite book |title=Iron in immunity, cancer, and inflammation |vauthors=Broc JH, De Sousa M |publisher=Wiley |year=1989 |isbn=978-0-471-92150-9 |location=New York}}</ref> The saturated iron concentration in lactoferrin in [[human milk]] is estimated as 10 to 30% (100% corresponds to all lactoferrin molecules containing 2 iron atoms). It is demonstrated that lactoferrin is involved not only in the transport of iron, zinc and copper, but also in the regulation of their intake.<ref name="pmid1581301">{{Cite journal |vauthors=Shongwe MS, Smith CA, Ainscough EW, Baker HM, Brodie AM, Baker EN |date=May 1992 |title=Anion binding by human lactoferrin: results from crystallographic and physicochemical studies |journal=Biochemistry |volume=31 |issue=18 |pages=4451–8 |doi=10.1021/bi00133a010 |pmid=1581301}}</ref> Presence of loose ions of zinc and copper does not affect the iron binding ability of lactoferrin, and might even increase it.

===Polymeric forms===
Both in blood plasma and in secretory fluids lactoferrin can exist in different polymeric forms ranging from [[monomer]]s to [[tetramer]]s. Lactoferrin tends to polymerize both ''in vitro'' and ''in vivo'', especially at high concentrations.<ref Name=Sousa /> Several authors found that the dominant form of lactoferrin in physiological conditions is a tetramer, with the monomer:tetramer ratio of 1:4 at the protein concentrations of 10<sup>−5</sup> M.<ref name="Bennett">{{Cite journal |vauthors=Bennett RM, Davis J |date=January 1982 |title=Lactoferrin interacts with deoxyribonucleic acid: a preferential reactivity with double-stranded DNA and dissociation of DNA-anti-DNA complexes |journal=The Journal of Laboratory and Clinical Medicine |volume=99 |issue=1 |pages=127–38 |pmid=6274982}}</ref><ref name="pmid6979357">{{Cite journal |vauthors=Bagby GC, Bennett RM |date=July 1982 |title=Feedback regulation of granulopoiesis: polymerization of lactoferrin abrogates its ability to inhibit CSA production |journal=Blood |volume=60 |issue=1 |pages=108–12 |doi=10.1182/blood.V60.1.108.108 |pmid=6979357 |doi-access=free}}</ref><ref name="pmid7762423">{{Cite book |title=Lactoferrin Structure and Function |vauthors=Mantel C, Miyazawa K, Broxmeyer HE |year=1994 |isbn=978-0-306-44734-1 |series=Advances in, Experimental Medicine and Biology |volume=357 |pages=121–32 |chapter=Physical Characteristics and Polymerization During Iron Saturation of Lactoferrin, A Myelopoietic Regulatory Molecule with Suppressor Activity |doi=10.1007/978-1-4615-2548-6_12 |pmid=7762423}}</ref>

It is suggested that the [[oligomer]] state of lactoferrin is determined by its concentration and that [[polymerization]] of lactoferrin is strongly affected by the presence of Ca<sup>2+</sup> ions. In particular, monomers were dominant at concentrations below 10<sup>−10</sup>−10<sup>−11</sup> M in the presence of Ca<sup>2+</sup>, but they converted into tetramers at lactoferrin concentrations above 10<sup>−9</sup>−10<sup>−10</sup> M.<ref name=Bennett /><ref name="Furmanski">{{Cite journal |vauthors=Furmanski P, Li ZP, Fortuna MB, Swamy CV, Das MR |date=August 1989 |title=Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity |journal=The Journal of Experimental Medicine |volume=170 |issue=2 |pages=415–29 |doi=10.1084/jem.170.2.415 |pmc=2189405 |pmid=2754391}}</ref> [[Titer]] of lactoferrin in the blood corresponds to this particular "transition concentration" and thus lactoferrin in the blood should be presented both as a monomer and tetramer. Many functional properties of lactoferrin depend on its oligomeric state. In particular, monomeric, but not tetrameric lactoferrin can strongly bind to DNA.

== Function ==
Lactoferrin belongs to the [[innate immune system]]. Apart from its main biological function, namely binding and transport of iron ions, lactoferrin also has antibacterial, antiviral, [[antiparasitic]], catalytic, anti-cancer, and anti-allergic functions and properties.<ref>{{Cite journal |vauthors=Adlerova L, Bartoskova A, Faldyna M |year=2008 |title=Lactoferrin: a review |journal=Veterinarni Medicina |volume=53 |issue=9 |page=457 |doi=10.17221/1978-VETMED |doi-access=free }}</ref>

===Enzymatic activity of lactoferrin===
Lactoferrin hydrolyzes [[RNA]] and exhibits the properties of [[pyrimidine]]-specific secretory [[ribonuclease]]s {{Citation needed|reason=The claim of RNase activity needs a reference to research supporting it.|date=September 2024}}. In particular, by destroying the RNA genome, milk RNase inhibits reverse transcription of [[retrovirus]]es that cause [[breast cancer]] in mice.<ref name="pmid4139659">{{Cite journal |vauthors=McCormick JJ, Larson LJ, Rich MA |date=October 1974 |title=RNase inhibition of reverse transcriptase activity in human milk |journal=Nature |volume=251 |issue=5477 |pages=737–40 |bibcode=1974Natur.251..737M |doi=10.1038/251737a0 |pmid=4139659|s2cid=4160337 }}</ref> [[Parsi]] women in West [[India]] have the milk RNase level markedly lower than in other groups, and their [[breast cancer]] rate is three times higher than average.<ref name="pmid60710">{{Cite journal |vauthors=Das MR, Padhy LC, Koshy R, Sirsat SM, Rich MA |date=August 1976 |title=Human milk samples from different ethnic groups contain RNase that inhibits, and plasma membrane that stimulates, reverse transcription |journal=Nature |volume=262 |issue=5571 |pages=802–5 |bibcode=1976Natur.262..802D |doi=10.1038/262802a0 |pmid=60710|s2cid=4216981 }}</ref> Thus, [[ribonuclease]]s of milk, and lactoferrin in particular, might play an important role in [[pathogenesis]].

===Lactoferrin receptor===
The [[ITLN1|lactoferrin receptor]] plays an important role in the [[Internalization (sociology)|internalization]] of lactoferrin; it also facilitates absorption of iron ions by lactoferrin. It was shown that [[gene expression]] increases with age in the [[duodenum]] and decreases in the [[jejunum]].<ref>{{Cite journal |vauthors=Liao Y, Lopez V, Shafizadeh TB, Halsted CH, Lönnerdal B |date=November 2007 |title=Cloning of a pig homologue of the human lactoferrin receptor: expression and localization during intestinal maturation in piglets |journal=Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology |volume=148 |issue=3 |pages=584–90 |doi=10.1016/j.cbpa.2007.08.001 |pmc=2265088 |pmid=17766154}}</ref>
The moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase ([[GAPDH]]) has been demonstrated to function as a receptor for lactoferrin.<ref name="pmid22292499">{{cite journal | vauthors = Rawat P, Kumar S, Sheokand N, Raje CI, Raje M | title = The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor | journal = Biochemistry and Cell Biology | volume = 90 | issue = 3 | pages = 329–38 | date = June 2012 | pmid = 22292499 | doi = 10.1139/o11-058 }}</ref>

===Bone activity===
Ribonuclease-enriched lactoferrin has been used to examine how lactoferrin affects bone. Lactoferrin has shown to have positive effects on bone turnover. It has aided in decreasing bone resorption and increasing bone formation. This was indicated by a decrease in the levels of two bone resorption markers ([[deoxypyridinoline]] and [[N-terminal telopeptide|N-telopeptide]]) and an increase in the levels two bone formation markers ([[osteocalcin]] and [[alkaline phosphatase]]).<ref name="bone turnover">{{Cite journal |vauthors=Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS |date=September 2009 |title=Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women |journal=Osteoporosis International |volume=20 |issue=9 |pages=1603–11 |doi=10.1007/s00198-009-0839-8 |pmid=19172341|s2cid=10711802 }}</ref> It has reduced [[osteoclast]] formation, which signifies a decrease in pro-inflammatory responses and an increase in  anti-inflammatory responses <ref name="Inflammatory responses">{{Cite journal |vauthors=Bharadwaj S, Naidu TA, Betageri GV, Prasadarao NV, Naidu AS |date=November 2010 |title=Inflammatory responses improve with milk ribonuclease-enriched lactoferrin supplementation in postmenopausal women |journal=Inflammation Research |volume=59 |issue=11 |pages=971–8 |doi=10.1007/s00011-010-0211-7 |pmid=20473630|s2cid=3180066 }}</ref> which indicates a reduction in bone resorption as well.

===Interaction with nucleic acids===
One of the important properties of lactoferrin is its ability to bind with nucleic acids. The fraction of protein extracted from milk, contains 3.3% RNA,<ref name=Bennett />
but, the protein preferably binds to double-stranded DNA rather than single-stranded DNA. The ability of lactoferrin to bind DNA is used for its isolation and purification using [[affinity chromatography]] with columns containing immobilized DNA-containing [[sorbent]]s, such as [[agarose]] with the immobilized single-stranded DNA.<ref name="pmid3827843">{{Cite journal |vauthors=Rosenmund A, Kuyas C, Haeberli A |date=November 1986 |title=Oxidative radioiodination damage to human lactoferrin |journal=The Biochemical Journal |volume=240 |issue=1 |pages=239–45 |doi=10.1042/bj2400239 |pmc=1147399 |pmid=3827843}}</ref>

==Clinical significance==
[[File:Lactoferrin and an E. Coli siderophore.svg|alt= Lactoferrin is a protein found in the immune system, and is a common defense against bacterial infections, which it is able to do by binding to iron with a higher affinity than most proteins.|thumb|284x284px|Lactoferrin (larger protein) and a [[siderophore]] of ''E. coli'' (smaller protein) are shown. Lactoferrin is a protein found in the immune system, and is a common defense against bacterial infections. Lactoferrin restricts access to host iron by binding to iron with a higher affinity than bacterial proteins.<ref name="Levay_1995">{{Cite journal |vauthors=Levay PF, Viljoen M |date=January 1995 |title=Lactoferrin: a general review |url=http://www.haematologica.org/content/80/3/252.full.pdf+html |journal=Haematologica |volume=80 |issue=3 |pages=252–67 |pmid=7672721}}</ref>]]

===Antibacterial activity===
Lactoferrin's primary role is to sequester free iron, and in doing so remove essential substrate required for bacterial growth.<ref name="Farnaud">{{Cite journal |vauthors=Farnaud S, Evans RW |date=November 2003 |title=Lactoferrin--a multifunctional protein with antimicrobial properties |journal=Molecular Immunology |volume=40 |issue=7 |pages=395–405 |doi=10.1016/S0161-5890(03)00152-4 |pmid=14568385}}</ref> Antibacterial action of lactoferrin  is also explained by the presence of specific [[receptor (biochemistry)|receptor]]s on the cell surface of microorganisms. Lactoferrin binds to lipopolysaccharide of bacterial walls, and the oxidized iron part of the lactoferrin oxidizes bacteria via formation of [[peroxide]]s. This affects the membrane permeability and results in the cell breakdown ([[lysis]]).<ref Name=Farnaud />

Although lactoferrin also has other antibacterial mechanisms not related to iron, such as stimulation of phagocytosis,<ref name="pmid9691154">{{Cite journal |vauthors=Xanthou M |year=1998 |title=Immune protection of human milk |journal=Biology of the Neonate |volume=74 |issue=2 |pages=121–33 |doi=10.1159/000014018 |pmid=9691154|s2cid=46828227 }}</ref> the interaction with the outer bacterial membrane described above is the most dominant and most studied.<ref name="pmid8612745">{{Cite journal |vauthors=Odell EW, Sarra R, Foxworthy M, Chapple DS, Evans RW |date=March 1996 |title=Antibacterial activity of peptides homologous to a loop region in human lactoferrin |journal=FEBS Letters |volume=382 |issue=1–2 |pages=175–8 |doi=10.1016/0014-5793(96)00168-8 |pmid=8612745|s2cid=30937106 |doi-access=free }}</ref> Lactoferrin not only disrupts the membrane, but even penetrates into the cell. Its binding to the bacteria wall is associated with the specific [[peptide]] [[lactoferricin]], which is located at the N-lobe of lactoferrin and is produced by ''in vitro'' cleavage of lactoferrin with another protein, [[trypsin]].<ref name="pmid9588189">{{Cite journal |vauthors=Kuwata H, Yip TT, Yip CL, Tomita M, Hutchens TW |date=April 1998 |title=Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry |journal=Biochemical and Biophysical Research Communications |volume=245 |issue=3 |pages=764–73 |doi=10.1006/bbrc.1998.8466 |pmid=9588189}}</ref><ref name="Sojar">{{cite journal | vauthors = Sojar HT, Hamada N, Genco RJ | title = Structures involved in the interaction of Porphyromonas gingivalis fimbriae and human lactoferrin | journal = FEBS Letters | volume = 422 | issue = 2 | pages = 205–8 | date = January 1998 | pmid = 9490007 | doi = 10.1016/S0014-5793(98)00002-7 | s2cid = 25875928 | doi-access =  }}</ref> A mechanism of the antimicrobial action of lactoferrin has been reported as lactoferrin targets H<sup>+</sup>-ATPase and interferes with proton translocation in the cell membrane, resulting in a lethal effect ''in vitro''.<ref>{{cite journal | vauthors = Andrés MT, Fierro JF | title = Antimicrobial mechanism of action of transferrins: selective inhibition of H+-ATPase | journal = Antimicrobial Agents and Chemotherapy | volume = 54 | issue = 10 | pages = 4335–42 | date = October 2010 | pmid = 20625147 | pmc = 2944611 | doi = 10.1128/AAC.01620-09 }}</ref>

Lactoferrin prevents the attachment of ''[[H. pylori]]'' in the stomach, which in turn, aids in reducing digestive system disorders. Bovine lactoferrin has more activity against ''[[H. pylori]]'' than human lactoferrin.<ref>{{cite book | vauthors = Jellin JM, Batz F, Hitchens K | title = Natural Medicines Comprehensive Databas | year = 2007 | isbn = 978-0-9788205-3-4 | page = 915 | edition = 10th | publisher = Therapeutic Research Faculty }}</ref>

===Antiviral activity===
Lactoferrin in sufficient strength acts on a wide range of human and animal viruses based on DNA and RNA [[genome]]s,<ref name="vander">{{cite journal | vauthors = van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK | title = Antiviral activities of lactoferrin | journal = Antiviral Research | volume = 52 | issue = 3 | pages = 225–239 | date = December 2001 | pmid = 11675140 | doi = 10.1016/S0166-3542(01)00195-4 | citeseerx = 10.1.1.104.745 }}</ref> including the [[herpes simplex virus]] 1 and 2,<ref name="pmid7661698">{{cite journal | vauthors = Fujihara T, Hayashi K | title = Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection to mouse cornea | journal = Archives of Virology | volume = 140 | issue = 8 | pages = 1469–1472 | year = 1995 | pmid = 7661698 | doi = 10.1007/BF01322673 | s2cid = 4396295 }}</ref><ref name="Giansanti">{{cite journal | vauthors = Giansanti F, Rossi P, Massucci MT, Botti D, Antonini G, Valenti P, Seganti L | title = Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin | journal = Biochemistry and Cell Biology | volume = 80 | issue = 1 | pages = 125–130 | year = 2002 | pmid = 11908636 | doi = 10.1139/o01-208 }}</ref><ref>{{cite journal | vauthors = Krzyzowska M, Chodkowski M, Janicka M, Dmowska D, Tomaszewska E, Ranoszek-Soliwoda K, Bednarczyk K, Celichowski G, Grobelny J | title = Lactoferrin-Functionalized Noble Metal Nanoparticles as New Antivirals for HSV-2 Infection | journal = Microorganisms | volume = 10 | issue = 1 | pages = 110 | date = January 2022 | pmid = 35056558 | pmc = 8780146 | doi = 10.3390/microorganisms10010110 | doi-access = free }}</ref> [[cytomegalovirus]],<ref name="pmid7622881">{{cite journal | vauthors = Harmsen MC, Swart PJ, de Béthune MP, Pauwels R, De Clercq E, The TH, Meijer DK | title = Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro | journal = The Journal of Infectious Diseases | volume = 172 | issue = 2 | pages = 380–388 | date = August 1995 | pmid = 7622881 | doi = 10.1093/infdis/172.2.380 }}</ref> [[HIV]],<ref name=Giansanti /><ref name="Puddu">{{cite journal | vauthors = Puddu P, Borghi P, Gessani S, Valenti P, Belardelli F, Seganti L | title = Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection | journal = The International Journal of Biochemistry & Cell Biology | volume = 30 | issue = 9 | pages = 1055–1062 | date = September 1998 | pmid = 9785469 | doi = 10.1016/S1357-2725(98)00066-1 | hdl = 11573/83805 }}</ref> [[hepatitis C virus]],<ref name="pmid17241377">{{cite journal | vauthors = Azzam HS, Goertz C, Fritts M, Jonas WB | title = Natural products and chronic hepatitis C virus | journal = Liver International | volume = 27 | issue = 1 | pages = 17–25 | date = February 2007 | pmid = 17241377 | doi = 10.1111/j.1478-3231.2006.01408.x | s2cid = 7732075 | doi-access = free }}</ref><ref name="Nozaki">{{cite journal | vauthors = Nozaki A, Ikeda M, Naganuma A, Nakamura T, Inudoh M, Tanaka K, Kato N | title = Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein | journal = The Journal of Biological Chemistry | volume = 278 | issue = 12 | pages = 10162–10173 | date = March 2003 | pmid = 12522210 | doi = 10.1074/jbc.M207879200 | doi-access = free }}</ref> [[hantavirus]]es, [[rotavirus]]es, [[poliovirus]] type 1,<ref name="Arnold">{{cite journal | vauthors = Arnold D, Di Biase AM, Marchetti M, Pietrantoni A, Valenti P, Seganti L, Superti F | title = Antiadenovirus activity of milk proteins: lactoferrin prevents viral infection | journal = Antiviral Research | volume = 53 | issue = 2 | pages = 153–158 | date = February 2002 | pmid = 11750941 | doi = 10.1016/S0166-3542(01)00197-8 | hdl = 11573/250295 }}</ref> [[human respiratory syncytial virus]], [[murine leukemia virus]]es<ref name="Sojar" /> and [[Mayaro virus disease|Mayaro virus]].<ref>{{cite journal | vauthors = Carvalho CA, Sousa IP, Silva JL, Oliveira AC, Gonçalves RB, Gomes AM | title = Inhibition of Mayaro virus infection by bovine lactoferrin | journal = Virology | volume = 452-453 | pages = 297–302 | date = March 2014 | pmid = 24606707 | doi = 10.1016/j.virol.2014.01.022 | doi-access = free | url = https://www.arca.fiocruz.br/bitstream/icict/32053/2/F94-1-s2.0-S004268221400035X-main.pdf }}</ref> Activity against [[COVID-19]] has been speculated but not proven.<ref name="pmid32738305">{{cite journal | vauthors = Chang R, Ng TB, Sun WZ | title = Lactoferrin as potential preventative and adjunct treatment for COVID-19 | journal = International Journal of Antimicrobial Agents | volume = 56 | issue = 3 | pages = 106118 | date = September 2020 | pmid = 32738305 | pmc = 7390755 | doi = 10.1016/j.ijantimicag.2020.106118 }}</ref><ref name="pmid33199997">{{cite journal | vauthors = Wang Y, Wang P, Wang H, Luo Y, Wan L, Jiang M, Chu Y | title = Lactoferrin for the treatment of COVID-19 (Review) | journal = Experimental and Therapeutic Medicine | volume = 20 | issue = 6 | pages = 272 | date = December 2020 | pmid = 33199997 | pmc = 7664603 | doi = 10.3892/etm.2020.9402 }}</ref><ref name="pmid34413211">{{cite journal | vauthors = Mirabelli C, Wotring JW, Zhang CJ, McCarty SM, Fursmidt R, Pretto CD, Qiao Y, Zhang Y, Frum T, Kadambi NS, Amin AT, O'Meara TR, Spence JR, Huang J, Alysandratos KD, Kotton DN, Handelman SK, Wobus CE, Weatherwax KJ, Mashour GA, O'Meara MJ, Chinnaiyan AM, Sexton JZ | title = Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 118 | issue = 36 | date = September 2021 | pmid = 34413211 | pmc = 8433531 | doi = 10.1073/pnas.2105815118 | bibcode = 2021PNAS..11805815M | doi-access = free }}</ref><ref name="pmid34575388">{{cite journal | vauthors = Rosa L, Tripepi G, Naldi E, Aimati M, Santangeli S, Venditto F, Caldarelli M, Valenti P | title = Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study | journal = Journal of Clinical Medicine | volume = 10 | issue = 18 | date = September 2021 | page = 4276 | pmid = 34575388 | pmc = 8469309 | doi = 10.3390/jcm10184276 | doi-access = free }}</ref>

The most studied mechanism of antiviral activity of lactoferrin is its diversion of virus particles from the target cells. Many viruses tend to bind to the [[lipoprotein]]s of the cell membranes and then penetrate into the cell.<ref Name=Nozaki /> Lactoferrin binds to the same lipoproteins thereby repelling the virus particles. Iron-free apolactoferrin is more efficient in this function than hololactoferrin; and lactoferricin, which is responsible for antimicrobial properties of lactoferrin, shows almost no antiviral activity.<ref name=vander />

Beside interacting with the cell membrane, lactoferrin also directly binds to viral particles, such as the [[hepatitis]] viruses.<ref Name=Nozaki /> This mechanism is also confirmed by the antiviral activity of lactoferrin against rotaviruses,<ref name=Sojar /> which act on different cell types.

Lactoferrin also suppresses virus replication after the virus penetrated into the cell.<ref Name=Sojar /><ref name=Puddu /> Such an indirect antiviral effect is achieved by affecting  [[natural killer cell]]s, [[granulocyte]]s and [[macrophage]]s – cells, which play a crucial role in the early stages of viral infections, such as [[severe acute respiratory syndrome]] (SARS).<ref name="pmid15655079">{{cite journal | vauthors = Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP, Melendez AJ | title = Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome | journal = BMC Immunology | volume = 6 | pages = 2 | date = January 2005 | pmid = 15655079 | pmc = 546205 | doi = 10.1186/1471-2172-6-2 | doi-access = free }}</ref>

===Antifungal activity===
Lactoferrin and lactoferricin inhibit ''in vitro'' growth of ''Trichophyton mentagrophytes'', which are responsible for several skin diseases such as [[ringworm]].<ref name="pmid11020258">{{cite journal | vauthors = Wakabayashi H, Uchida K, Yamauchi K, Teraguchi S, Hayasawa H, Yamaguchi H | title = Lactoferrin given in food facilitates dermatophytosis cure in guinea pig models | journal = The Journal of Antimicrobial Chemotherapy | volume = 46 | issue = 4 | pages = 595–602 | date = October 2000 | pmid = 11020258 | doi = 10.1093/jac/46.4.595 | doi-access = free }}</ref> Lactoferrin also acts against the ''[[Candida albicans]]'' – a [[diploid]] [[fungus]] (a form of [[yeast]]) that causes [[Opportunistic infection|opportunistic]] oral and [[genital]] infections in humans.<ref name="Lupetti">{{cite journal | vauthors = Lupetti A, Paulusma-Annema A, Welling MM, Dogterom-Ballering H, Brouwer CP, Senesi S, Van Dissel JT, Nibbering PH | title = Synergistic activity of the N-terminal peptide of human lactoferrin and fluconazole against Candida species | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 1 | pages = 262–7 | date = January 2003 | pmid = 12499200 | pmc = 149030 | doi = 10.1128/AAC.47.1.262-267.2003 }}</ref><ref name="Viejo">{{cite journal | vauthors = Viejo-Díaz M, Andrés MT, Fierro JF | title = Modulation of in vitro fungicidal activity of human lactoferrin against Candida albicans by extracellular cation concentration and target cell metabolic activity | journal = Antimicrobial Agents and Chemotherapy | volume = 48 | issue = 4 | pages = 1242–8 | date = April 2004 | pmid = 15047526 | pmc = 375254 | doi = 10.1128/AAC.48.4.1242-1248.2004 }}</ref> [[Fluconazole]] has long been used against ''Candida albicans'', which resulted in emergence of [[strain (biology)|strains]] resistant to this drug. However, a combination of lactoferrin with fluconazole can act against fluconazole-resistant strains of ''Candida albicans'' as well as other types of [[Candida (genus)|Candida]]: ''C. glabrata, C. krusei, C. parapsilosis'' and ''C. tropicalis''.<ref name=Lupetti /> Antifungal activity is observed for sequential incubation of ''Candida'' with lactoferrin and then with fluconazole, but not vice versa. The antifungal activity of lactoferricin exceeds that of lactoferrin. In particular, synthetic peptide 1–11 lactoferricin shows much greater activity against ''Candida albicans'' than native lactoferricin.<ref name=Lupetti />

Administration of lactoferrin through drinking water to mice with weakened immune systems and symptoms of [[aphthous ulcer]] reduced the number of ''Candida albicans'' strains in the mouth and the size of the damaged areas in the tongue.<ref name="pmid12878528">{{cite journal | vauthors = Takakura N, Wakabayashi H, Ishibashi H, Teraguchi S, Tamura Y, Yamaguchi H, Abe S | title = Oral lactoferrin treatment of experimental oral candidiasis in mice | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 8 | pages = 2619–23 | date = August 2003 | pmid = 12878528 | pmc = 166093 | doi = 10.1128/AAC.47.8.2619-2623.2003 }}</ref> Oral administration of lactoferrin to animals also reduced the number of pathogenic organisms in the tissues close to the [[gastrointestinal tract]]. ''Candida albicans'' could also be completely eradicated with a mixture containing lactoferrin, [[lysozyme]] and [[itraconazole]] in HIV-positive patients who were resistant to other antifungal drugs.<ref name="pmid11089630">{{cite journal | vauthors = Masci JR | title = Complete response of severe, refractory oral candidiasis to mouthwash containing lactoferrin and lysozyme | journal = AIDS | volume = 14 | issue = 15 | pages = 2403–4 | date = October 2000 | pmid = 11089630 | doi = 10.1097/00002030-200010200-00023 | doi-access = free }}</ref> Such antifungal action when other drugs deem inefficient is characteristic of lactoferrin and is especially valuable for HIV-infected patients.<ref name="pmid10543740">{{cite journal | vauthors = Kuipers ME, de Vries HG, Eikelboom MC, Meijer DK, Swart PJ | title = Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 11 | pages = 2635–41 | date = November 1999 | pmid = 10543740 | pmc = 89536 | doi = 10.1128/AAC.43.11.2635 }}</ref> Contrary to the antiviral and antibacterial actions of lactoferrin, very little is known about the mechanism of its antifungal action. Lactoferrin seems to bind the [[plasma membrane]] of ''C. albicans'' inducing an apoptotic-like process.<ref name=Viejo /><ref>{{cite journal | vauthors = Andrés MT, Viejo-Díaz M, Fierro JF | title = Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical role of K+-channel-mediated K+ efflux | journal = Antimicrobial Agents and Chemotherapy | volume = 52 | issue = 11 | pages = 4081–8 | date = November 2008 | pmid = 18710913 | doi = 10.1128/AAC.01597-07 | pmc = 2573133 }}</ref>

===Anticarcinogenic activity===
The [[anticancer]] activity of [[bovine]] lactoferrin (bLF) has been demonstrated in experimental lung, bladder, tongue, colon, and liver carcinogeneses on rats, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 ([[CYP1A2]]).<ref name="pmid11908637">{{cite journal | vauthors = Tsuda H, Sekine K, Fujita K, Ligo M | title = Cancer prevention by bovine lactoferrin and underlying mechanisms--a review of experimental and clinical studies | journal = Biochemistry and Cell Biology | volume = 80 | issue = 1 | pages = 131–6 | year = 2002 | pmid = 11908637 | doi = 10.1139/o01-239 }}</ref> Also, in another experiment done on [[hamsters]], bovine lactoferrin decreased the incidence of [[oral cancer]] by 50%.<ref name="pmid16928475"/> Currently, bLF is used as an ingredient in [[yogurt]], [[chewing gums]], [[infant formulas]], and [[cosmetics]].<ref name="pmid16928475">{{cite journal | vauthors = Chandra Mohan KV, Kumaraguruparan R, Prathiba D, Nagini S | title = Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin | journal = Nutrition | volume = 22 | issue = 9 | pages = 940–6 | date = September 2006 | pmid = 16928475 | doi = 10.1016/j.nut.2006.05.017 }}</ref>

===Cystic fibrosis===
The human lung and saliva contain a wide range of antimicrobial compound including lactoperoxidase system, producing [[hypothiocyanite]] and lactoferrin, with hypothiocyanite missing in [[cystic fibrosis]] patients.<ref name="pmid17082494">{{cite journal | vauthors = Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB, Nauseef WM, Dupuy C, Bánfi B | title = A novel host defense system of airways is defective in cystic fibrosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 175 | issue = 2 | pages = 174–83 | date = January 2007 | pmid = 17082494 | pmc = 2720149 | doi = 10.1164/rccm.200607-1029OC }}</ref> Lactoferrin, a component of innate immunity, prevents bacterial [[biofilm]] development.<ref name="pmid11048725">{{cite journal | vauthors = Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP | title = Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms | journal = Nature | volume = 407 | issue = 6805 | pages = 762–4 | date = October 2000 | pmid = 11048725 | doi = 10.1038/35037627 | bibcode = 2000Natur.407..762S | s2cid = 4372096 }}</ref><ref name="pmid12037568">{{cite journal | vauthors = Singh PK, Parsek MR, Greenberg EP, Welsh MJ | title = A component of innate immunity prevents bacterial biofilm development | journal = Nature | volume = 417 | issue = 6888 | pages = 552–5 | date = May 2002 | pmid = 12037568 | doi = 10.1038/417552a | bibcode = 2002Natur.417..552S | s2cid = 4423528 }}</ref> The loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity is observed in patients with cystic fibrosis.<ref name="pmid15346334">{{cite journal | vauthors = Rogan MP, Taggart CC, Greene CM, Murphy PG, O'Neill SJ, McElvaney NG | title = Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis | journal = The Journal of Infectious Diseases | volume = 190 | issue = 7 | pages = 1245–53 | date = October 2004 | pmid = 15346334 | doi = 10.1086/423821 | doi-access = free }}</ref> In cystic fibrosis, antibiotic susceptibility may be modified by lactoferrin.<ref>{{cite journal | vauthors = Andrés MT, Viejo-Diaz M, Pérez F, Fierro JF | title = Antibiotic tolerance induced by lactoferrin in clinical Pseudomonas aeruginosa isolates from cystic fibrosis patients | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 4 | pages = 1613–6 | date = April 2005 | pmid = 15793153 | doi = 10.1128/aac.49.4.1613-1616.2005 | pmc = 1068597 }}</ref> These findings demonstrate the important role of lactoferrin in human host defense and especially in lung.<ref name="pmid16503962">{{cite journal | vauthors = Rogan MP, Geraghty P, Greene CM, O'Neill SJ, Taggart CC, McElvaney NG | title = Antimicrobial proteins and polypeptides in pulmonary innate defence | journal = Respiratory Research | volume = 7 | issue = 1 | pages = 29 | date = February 2006 | pmid = 16503962 | pmc = 1386663 | doi = 10.1186/1465-9921-7-29 | doi-access = free }}</ref> Lactoferrin with hypothiocyanite has been granted [[orphan drug]] status by the [[European Medicines Agency|EMEA]]<ref name="urlwww.ema.europa.eu">{{cite web|url = http://www.ema.europa.eu/pdfs/human/comp/opinion/39298409en.pdf|title = Public summary of positive opinion for orphan designation of hypothiocyanite/lactoferrin for the treatment of cystic fibrosis|date = 2009-09-07|work = Pre-authorisation Evaluation of Medicines for Human Use|publisher = European Medicines Agency|access-date = 2010-01-23|url-status = dead|archive-url = https://web.archive.org/web/20100530100046/http://www.ema.europa.eu/pdfs/human/comp/opinion/39298409en.pdf|archive-date = 2010-05-30}}</ref> and the [[Food and Drug Administration (United States)|FDA]].<ref name="urlwww.bioalaxia.eu">{{cite web|url = http://www.bioalaxia.eu/content/meveol-orphan-drug-status-granted-fda-treatment-cystic-fibrosis|title = Meveol: orphan drug status granted by the FDA for the treatment of cystic fibrosis|date = 2009-11-05|publisher = United States Food and Drug Administration|access-date = 2010-01-23|url-status = dead|archive-url = https://web.archive.org/web/20091224145219/http://www.bioalaxia.eu/content/meveol-orphan-drug-status-granted-fda-treatment-cystic-fibrosis|archive-date = 2009-12-24}}</ref>

===Necrotizing enterocolitis===
Low quality evidence suggests that oral lactoferrin supplementation with or without the addition of a probiotic may decrease late onset of sepsis and [[necrotizing enterocolitis]] (stage II or III) in preterm infants with no adverse effects.<ref>{{cite journal | vauthors = Pammi M, Suresh G | title = Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 3 | pages = CD007137 | date = March 2020 | issue = 3 | pmid = 32232984 | pmc = 7106972 | doi = 10.1002/14651858.CD007137.pub6 }}</ref>

===In diagnosis===
Lactoferrin levels in tear fluid have been shown to decrease in dry eye diseases such as [[Sjögren's syndrome]].<ref>{{cite journal | vauthors = Ohashi Y, Ishida R, Kojima T, Goto E, Matsumoto Y, Watanabe K, Ishida N, Nakata K, Takeuchi T, Tsubota K | title = Abnormal protein profiles in tears with dry eye syndrome | journal = American Journal of Ophthalmology | volume = 136 | issue = 2 | pages = 291–9 | date = August 2003 | pmid = 12888052 | doi = 10.1016/S0002-9394(03)00203-4 }}</ref> A rapid, portable test utilizing microfluidic technology has been developed to enable measurement of lactoferrin levels in human tear fluid at the point-of-care with the aim of improving diagnosis of Sjögren's syndrome and other forms of dry eye disease.<ref>{{cite journal | vauthors = Karns K, Herr AE | title = Human tear protein analysis enabled by an alkaline microfluidic homogeneous immunoassay | journal = Analytical Chemistry | volume = 83 | issue = 21 | pages = 8115–22 | date = November 2011 | pmid = 21910436 | doi = 10.1021/ac202061v }}</ref>

==Technology==

===Extraction===
Bovine lactoferrin can be isolated from raw milk, colostrum, or [[whey]] using methods such as salt extraction, chromatography, and membrane filtration. Lactoferrin from a variety of species, including humans, can also be produced using transgenic organisms as a [[recombinant protein]].<ref>{{cite journal|doi=10.1002/fbe2.12003 |title=Recent advances and prospects in purification and heterologous expression of lactoferrin |date=2022 | vauthors = Cui S, Lv X, Sun G, Wu W, Xu H, Li Y, Liu Y, Li J, Du G, Wang M, Liu  |journal=Food Bioengineering |volume=1 |pages=58–67 |doi-access=free }}</ref>

===Nanotechnology===
Lactotransferrin has been used in the synthesis of fluorescent gold quantum clusters, which has potential applications in nanotechnology.<ref name="pmid20882247">{{cite journal | vauthors = Xavier PL, Chaudhari K, Verma PK, Pal SK, Pradeep T | title = Luminescent quantum clusters of gold in transferrin family protein, lactoferrin exhibiting FRET | journal = Nanoscale | volume = 2 | issue = 12 | pages = 2769–76 | date = December 2010 | pmid = 20882247 | doi = 10.1039/C0NR00377H | bibcode = 2010Nanos...2.2769X | url = http://repository.ias.ac.in/82425/1/27-p.pdf }}</ref>

== See also ==
*[[Respiratory tract antimicrobial defense system]]

== References ==
{{reflist|32em}}

== External links ==
*[https://www.uniprot.org/uniprot/P02788 Uniprot]
*[https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=4057 LTF on the National Center for Biotechnology Information]
*[https://www.fda.gov/bbs/topics/NEWS/2003/NEW00935.html FDA]{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} Lactoferrin Considered Safe to Fight E. Coli.

{{PDB Gallery|geneid=4057}}
{{Globulins}}
{{Iron-binding proteins}}
{{Glycoproteins}}
{{Granule contents}}

[[Category:Glycoproteins]]
[[Category:Transferrins]]