Open Access Open Access  Restricted Access Subscription or Fee Access

Lactoferrin: An Overview

Daddaladka Krishnayya Samartha, Halugudde Nagaraja Sarjan

Abstract


Lactoferrin (Lf) is an iron-binding glycoprotein synthesized predominantly in mammary glands of animals. Lf is majorly found in milk and colostrum of livestock and mouse. The presence of Lf in indigenous breeds of cattle has a significant role in exerting immunoprotection. Studies have highlighted the significant activities of Lf viz., anti-parasitic, antioxidant, anti-cancer, anti-inflammatory, antimicrobial, and growth factor activator in cell cultures. The capacity of Lf to bind to different types of cells enhances its ability to prevent free radical-mediated damage or microbial invasion. However, further studies involving Lf-cell interactions will reveal its molecular insights towards antimicrobial, immune-modulatory, and anti-neoplastic properties.

Keywords


Anti-oxidant, bovine, cattle, colostrum, lactoferrin, milk

Full Text:

PDF

References


Giansanti F, Panella G, Leboffe L, Antonini G. Lactoferrin from milk: nutraceutical and pharmacological properties. Pharmaceu. 2016; 9(4): 61. DOI: 10.3390/ph9040061.

Johanson B. Isolation of an iron containing red protein from human milk. Acta Chemica Scandinavica. 1960; 14: 510–512.

Montreuil J, Tonnelat J, Mullet S. Preparation and properties of lactosiderophilin (lactotransferrin) of human milk. Biochimica et Biophysica Acta. 1960; 45: 413–421.

Moore SA, Anderson BF, Groom CR, Haridas M, Baker EN. Three dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution. J. Mol. Biol. 1997; 274: 222–236.

Anderson BF, Baker HM, Dodson EJ, Norris GE, Rumball SV, Waters JM, Baker EN. Structure of human lactoferrin at 3.2-Å resolution. Proc. Natl. Acad. Sci. USA. 1987; 84: 1769–1773.

Baker EN, Baker HM. Molecular structure, binding properties and dynamics of lactoferrin. Cel¬lular and Molecular Life Sciences. 2005; 62: 2531–2539.

Aisen P, Harris DC. Physical biochemistry of the transferrins. In: Loehr T (ed.). Iron Carriers and Iron Proteins. NY, USA: VCH Publishers; 1989. pp. 241–251.

Furmanski P, Li ZP, Fortuna MB, Swamy CVB, Das MR. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. The J of Expt Med. 1989; 170: 415–429.

Metz-Boutique MH, Jolles J, Mazurier J, Schoentgen F, Legrand D, Spik G, Montreuil J, Jolles P. Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. European J of Biochemistry. 1984; 145: 659–676.

Zheng J, Ather JL, Sonstegard TS, Kerr DE. Characterization of the infection-responsive bovine lactoferrin promoter. Gene. 2005; 353(1): 107–117.

Connely OM. Anti-inflammatory activities of lactoferrin. J. Am. Coll. Nutr. 2001; 20: 389S–395S.

Rodriguez DA, Vazquez L, Ramos G. Antimicrobial mechanisms and potential clinical application of lactoferrin. Rev. Latino. Microbiol. 2005; 47: 102–111.

Steijns JM, Hooijdonk ACV. Occurrence, structure, biochemical properties and technological characteristics of lactoferrin. British J. of Nutr. 2000; 84(1): S11–S17.

Arnold R, Pruitt KM, Cole MF, Adamson JM, McGhee JR. Salivary antibacterial mechanisms in immunodeficiency. In Kleinberg I, Ellison SA, Mandel ID, (editors). Saliva and Dental Caries. New York, N.Y: Information Retrieval Inc.; 1979. pp. 449–462.

Renner E, Schaafsma G, Scott KJ. Micronutrients in milk. In: Renner E (ed.). Micronutrients in milk and milk-based food products. Barking, UK: Elsevier Applied Sciences Publishers; 1989. pp. 1–70.

Levay PF, Viljoen M. Lactoferrin: A general review. Haematologica. 1995; 80: 252–267.

Tsuji, S., Hirata, Y., Mukai, F. and Ohtagaki, S., 1990. Comparison of lactoferrin content in colostrum between different cattle breeds. Journal of Dairy Science, 73(1), pp.125-128.

Rachman AB, Maheswari RR, Bachroem MS. Composition and isolation of lactoferrin from colostrum and milk of various goat breeds. Procedia Food Sci. 2015; 3: 200–210.

Yoshida S, Wei Z, Shinmura Y, Fukunaga N. Separation of lactoferrin-a and -b from bovine colostrum. J of Dairy Sci. 2000; 83: 2211–2215.

Ferrer PAR, Baroni A, Sambucetti ME, Lo´pez NE, Dan JMC, Cernadas MD. Lactoferrin levels in term and preterm milk. J of the American College of Nutr. 2000; 19(3): 370–373.

Sharma A, Shandilya UK, Sodhi M, Mohanty AK, Jain P, Mukesh M. Evaluation of milk colostrum derived lactoferrin of Sahiwal (Bos indicus) and Karan Fries (cross-bred) cows for its anti-cancerous potential. Int. J. Mol. Sci.; 2020(24): 6318. DOI: 10.3390/ijms20246318.

Hagiwara SI, Kawai K, Nagahata H. Lactoferrin concentrations in milk from normal and subclinical mastitic cows. J. Vet. Med. Sci. 2003; 65(3): 319–323.

Welty FK, Smith KL, Schanbacher FL. Lactoferrin concentration during involution of the bovine mammary gland. J of Dairy Sci. 1976; 59(2): 224–231.

Stelwagen K, Carpenter E, Haigh B, Hodgkinson A, Wheeler TT. Immune components of bovine colostrum and milk. J. Anim. Sci. 2009; 87: 3–9.

Singh AP, Ramesha KP, Mir MA, Arya A, Isloor S. Variation in lactoferrin gene affects milk lactoferrin content and somatic cell count in Murrah buffaloes. Indian J. of Animal Research. 2019. DOI: 10.18805/ijar.B-3773.

Snick VJL, Masson PL, Heremans JF. The involvement of lactoferrin in the hyposideremia of acute inflammation. The J of Expt Med. 1974; 140: 1068–1084.

Iyer S, Lonnerdal B. Lactoferrin, lactoferrin receptors and iron metabolism. European J of Clinical Nutr. 1993; 47: 232–241.

Maher RJ, Cao D, Boxer LA, Petty HR. Simultaneous calcium dependent delivery of neutrophil lactoferrin and reactive oxygen metabolites to erythrocyte targets: evidence supporting granule-dependent triggering of superoxide deposition. J Cell Physiol. 1993; 156: 226–234.

Masson PL, Heremans JF, Schonne E. Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med. 1969; 130(3): 643–658.

Hutchens TW, Henry JF, Yip TT, et al. Origin of intact lactoferrin and its DNA binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. Pediatr Res. 1991; 29: 243–250.

Sanchez L, Lujan L, Oria R, Castillo H, Perez D, Ena JM, Calvo H. Synthesis of lactoferrin and transport of transferrin in the lactating mammary gland of sheep. J Dairy Sci. 1992. 75: 1257–1262.

Otsuki K, Yoda A, Mitsuhashik Y, Shimizu Y, Saito, H, Yanaihara T, Makino Y. Isolation and detection of human lactoferrin binding protein in human amniotic membrane. Excerpta Medica International Congress Series. 2000; 1195: 343–346.

Legrand D, Mazurier J, Elass A, Rochard E, Vergoten G, Maes P, Montreuil J, Spik G. Molecular interactions between human lactotransferrin and the phytohemagglutinin-activated human lymphocyte lactotransferrin receptor lie in two loop-containing regions of the N-terminal domain I of human lactotransferrin. Biochemistry. 1992; 31: 9243–9251.

Brock J. Lactoferrin structure-function relationships: An overview. Experimental Biology and Medicine. 1997; 28: 3–23.

Wong WP, Ligo M, Sato J, Sekine K, Adachi I, Tsuda H. Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Japanese Journal of Cancer Research. 2000; 91: 1022–1027.

Leveugle B, Mazurier J, Legrand D, Mazurier C, Montreuil J, Spik G. Lactotransferrin binding to its platelet receptor inhibits platelet aggregation. European J of Biochemistry. 1993; 213: 1205–1211.

Sitaram MP, McAbee DD. Isolated rat hepatocytes differentially bind and internalize bovine lactoferrin N-and C-lobes. Biochemical Journal. 1997; 323: 815–822.

Sorensen M, Sorensen SPL. The proteins in whey. comptes-rendus des travaux du laboratoire Carlsberg. 1939; 23: 55–99.

Lepanto MS, Rosa L, Paesano R, Valenti P, Cutone A. Lactoferrin in aseptic and septic inflammation. Molecules. 2019; 24(7): 1323. DOI: 10.3390/molecules24071323.

Reghunathan R, Jayapal M, Hsu LY, Chang HH, Tai D, Leung BP, et al. Expression profile of immune response genes in patients with severe acute respiratory syndrome. BMC Immunol. 2005; 6: 2. DOI: 10.1186/1471-2172-6-2.

Lang J, Yang N, Deng J, Liu K, Yang P, Zhang G, et al. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS One. 2011; 6: e23710. DOI: 10.1371/journal.pone.0023710.

Redwan EM, Uversky VN, El-Fakharany, EM, Al-Mehdar, H. Potential lactoferrin activity against pathogenic viruses. C R Biol. 2014; 337: 581–595. DOI: 10.1016 j.crvi.2014.08.003.

Carvalho CAM, Casseb SMM, Goncalves RB, Silva EVP, Gomes AMO, Vasconcelos PFC. Bovine lactoferrin activity against chikungunya and zika viruses. J Gen Virol. 2017; 98: 1749–1754. DOI:10.1099/jgv.0.000849.

Sharma S, Sinha M, Kaushik S, Kaur P, Singh TP. C-lobe of lactoferrin: The whole story of the half-molecule. 2013; 2013.

Omata Y, Satake M, Maeda R, et al. Reduction of the infectivity of Toxoplasma gondii and Eimeria stiedai sporozoites by treatment with bovine lactoferricin. The J of Vet Med Sci. 2001; 63(2): 187–190.

Cirioni O, Giacometti A, Barchiesi F, Scalise G. Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline. The J of Antimicrobial Chemotherapy. 2000; 46: 577–582.

Hagiwara T, Shinoda I, Fukuwatari Y, Shimamura S. Effect of lactoferrin and its peptides on pro¬liferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor. Bioscience, Biotechnology, and Biochemistry. 1995; 59: 1875–1881.

Yanaihara A, Toma Y, Saito H, Yanaihara T. Cell proliferation effect of lactoferrin in human endometrial stroma cells. Molecular Human Reproduction. 2000; 6: 469–473.

Bezault J, Bhimani R, Wiprovnick J, Furmanski P. Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice. Cancer Research. 1994; 54: 2310–2312.

Wolf JS, Li D, Taylor RJ, O’Malley BW Jr. Lactoferrin inhibits growth of malignant tumors of the head and neck. ORL: Journal for Oto-Rhino-Laryngology and its Related Specialties. 2003; 65(5): 245–249.

Damiens E, Yazidi I, Mazurier J, Duthille I, Spik G, Marer BY. Lactoferrrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. Journal of Cellular Biochemistry. 1999; 74: 486–498.

Cornish J, Callon KE, Naot D, Palmano KP, Banovic T, Bava U, Watson M, Lin JM, Tong PC, Chen Q, Chan VA, Reid HE, Fazzalari N, Baker HM, Baker EN, Haggararty NW, Grey AB, Reid IR. Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology. 2004; 145: 4366–4374.

Devi AS, Das MR, Pandit MW. Lactoferrin contains structural motifs of ribonuclease. Biochimica et Biophysica Acta. 1994; 1205: 275–281.

He J, Furmanski P. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature. 1995; 373: 721–724.

Giacinti G, Basirico L, Ronchi B, Bernabucci U. Lactoferrin concentration in buffalo milk. Ital J Anim Sci. 2013; 12: e23.

Korhonen H. Antimicrobial factors in bovine colostrum. Journal of the Scientific Agricultural Society of Finland. 1977; 49: 434–447.


Refbacks

  • There are currently no refbacks.