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A critical review of the roles of host lactoferrin in immunity

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Abstract

Lactoferrin (Lf) is an essential element of innate immunity, which refers to antigen-nonspecific defense mechanisms that a host uses immediately or within hours after exposure to an antigen. Following infection, Lf is released from neutrophils (PMNs) in blood and inflamed tissues and, such as other soluble pattern-recognition receptors of the innate immunity, Lf recognizes unique microbial molecules called pathogen-associated molecular patterns (PAMPs): LPS from the gram-negative cell wall and bacterial unmethylated CpG DNA. However, unlike classical PAMPs receptors involved in the activation of immune cells, Lf may act either as a competitor for these receptors or as a partner molecule, depending on the physiological status of the organism. These immunomodulatory properties are explained by the ability of Lf to interact with proteoglycans and receptors on the surface of mammalian cells: cells of the innate (NK cells, neutrophils, macrophages, basophils, neutrophils and mast cells) and adaptive [lymphocytes and antigen-presenting cells (APCs)] immune systems, and also epithelial and endothelial cells. Through these interactions, Lf is able to modulate the migration, maturation and functions of immune cells, and thus to influence both adaptive and innate immunities. The understanding of the roles of the host-expressed Lf in immunity comes from in vivo and in vitro studies with exogenous Lf which, although informative, rarely reflect the pathological, or non-pathological, conditions in the organism. In this review, the data from the literature will be critically analyzed in order to present a real picture of the regulatory roles of host Lf in immunity.

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References

  • Akira S, Hemmi H (2003) Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett 85:85–95

    Article  CAS  PubMed  Google Scholar 

  • Annane D, Bellisant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78

    Article  CAS  PubMed  Google Scholar 

  • Appelmelk BJ, An YQ, Geerts M, Thijs BG, de Boer HA, MacLaren DM, de Graaff J, Nuijens JH (1994) Lactoferrin is a lipid A-binding protein. Infect Immun 62:2628–2632

    CAS  PubMed  Google Scholar 

  • Artym J, Zimecki M, Kruzel ML (2003a) Reconstitution of the cellular immune response by lactoferrin in cyclophosphamide-treated mice is correlated with renewal of T cell compartment. Immunobiology 207:197–205

    Article  CAS  PubMed  Google Scholar 

  • Artym J, Zimecki M, Paprocka M, Kruzel ML (2003b) Orally administered lactoferrin restores humoral immune response in immunocompromised mice. Immunol Lett 89:9–15

    Article  CAS  PubMed  Google Scholar 

  • Artym J, Zimecki M, Kruzel ML (2004) Effects of lactoferrin on IL-6 production by peritoneal and alveolar cells in cyclophosphamide-treated mice. J Chemother 16:187–192

    CAS  PubMed  Google Scholar 

  • Baveye S, Elass E, Fernig DG, Blanquart C, Mazurier J, Legrand D (2000a) Human lactoferrin interacts with soluble CD14 and inhibits expression of endothelial adhesion molecules, E-selectin and ICAM-1, induced by the CD14-lipopolysaccharide complex. Infect Immun 68:6519–6525

    Article  CAS  PubMed  Google Scholar 

  • Baveye S, Elass E, Mazurier J, Legrand D (2000b) Lactoferrin inhibits the binding of lipopolysaccharides to L-selectin and subsequent production of reactive oxygen species by neutrophils. FEBS Lett 469:5–8

    Article  CAS  PubMed  Google Scholar 

  • Bennett RM, Kokocinski T (1978) Lactoferrin content of peripheral blood cells. Br J Haematol 39:509–521

    Article  CAS  PubMed  Google Scholar 

  • Bi BY, Lefebvre AM, Dus D, Spik G, Mazurier J (1997) Effect of lactoferrin on proliferation and differentiation of the Jurkat human lymphoblastic T cell line. Arch Immunol Ther Exp (Warsz) 45:315–320

    CAS  Google Scholar 

  • Bournazou I, Mackenzie KJ, Duffin R, Rossi AG, Gregory CD (2009) Inhibition of eosinophil migration by lactoferrin. Immunol Cell Biol (in press). DOI 10.1038/icb.2009.86

  • Breton-Gorius J, Mason DY, Buriot D, Vilde JL, Griscelli C (1980) Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. Detection by immunoperoxidase staining for lactoferrin and cytochemical electron microscopy. Am J Pathol 99:413–428

    CAS  PubMed  Google Scholar 

  • Britigan BE, Lewis TS, Waldschmidt M, McCormick ML, Krieg AM (2001) Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. J Immunol 167:2921–2928

    CAS  PubMed  Google Scholar 

  • Chodaczek G, Zimecki M, Lukasiewicz J, Lugowski C (2006) A complex of lactoferrin with monophosphoryl lipid A is an efficient adjuvant of the humoral and cellular immune response in mice. Med Microbiol Immunol 195:207–216

    Article  CAS  PubMed  Google Scholar 

  • Chodaczek G, Zimecki M, Lukasiewicz J, Lugowski C (2008) Lactoferrin-monophosphoryl lipid A complex enhances immunity of mice to Plesiomonas shigelloides CNCTC 138/92. Acta Biochim Pol 55:91–96

    CAS  PubMed  Google Scholar 

  • Crouch SP, Slater KJ, Fletcher J (1992) Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 80:235–240

    CAS  PubMed  Google Scholar 

  • Cumberbatch M, Bhushan M, Dearman RJ, Kimber I, Griffiths CE (2003) IL-1beta-induced Langerhans’ cell migration and TNF-alpha production in human skin: regulation by lactoferrin. Clin Exp Immunol 132:352–359

    Article  CAS  PubMed  Google Scholar 

  • Curran CS, Demick KP, Mansfield JM (2006) Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Cell Immunol 242:23–30

    Article  CAS  PubMed  Google Scholar 

  • de la Rosa G, Yang D, Tewary P, Varadhachary A, Oppenheim JJ (2008) Lactoferrin acts as an alarmin to promote the recruitment and activation of APCs and antigen-specific immune responses. J Immunol 180:6868–6876

    PubMed  Google Scholar 

  • Debanne MT, Regoeczi E, Sweeney GD, Krestynski F (1985) Interaction of human lactoferrin with the rat liver. Am J Physiol 248:G463–G469

    CAS  PubMed  Google Scholar 

  • Deriy LV, Chor J, Thomas LL (2000) Surface expression of lactoferrin by resting neutrophils. Biochem Biophys Res Commun 275:241–246

    Article  CAS  PubMed  Google Scholar 

  • Dhennin-Duthille I, Masson M, Damiens E, Fillebeen C, Spik G, Mazurier J (2000) Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line. J Cell Biochem 79:583–593

    Article  CAS  PubMed  Google Scholar 

  • Dial EJ, Dohrman AJ, Romero JJ, Lichtenberger LM (2005) Recombinant human lactoferrin prevents NSAID-induced intestinal bleeding in rodents. J Pharm Pharmacol 57:93–99

    Article  CAS  PubMed  Google Scholar 

  • Elass E, Masson M, Mazurier J, Legrand D (2002) Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells. Infect Immun 70:1860–1866

    Article  CAS  PubMed  Google Scholar 

  • Elass-Rochard E, Roseanu A, Legrand D, Trif M, Salmon V, Motas C, Montreuil J, Spik G (1995) Lactoferrin-lipopolysaccharide interaction: involvement of the 28–34 loop region of human lactoferrin in the high-affinity binding to Escherichia coli 055B5 lipopolysaccharide. Biochem J 312:839–845

    CAS  PubMed  Google Scholar 

  • Elass-Rochard E, Legrand D, Salmon V, Roseanu A, Trif M, Tobias PS, Mazurier J, Spik G (1998) Lactoferrin inhibits the endotoxin interaction with CD14 by competition with the lipopolysaccharide-binding protein. Infect Immun 66:486–491

    CAS  PubMed  Google Scholar 

  • Elrod KC, Moore WR, Abraham WM, Tanaka RD (1997) Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. Am J Respir Crit Care Med 156:375–381

    CAS  PubMed  Google Scholar 

  • Fischer R, Debbabi H, Dubarry M, Boyaka P, Tome D (2006) Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin. Biochem Cell Biol 84:303–311

    Article  CAS  PubMed  Google Scholar 

  • Gahr M, Speer CP, Damerau B, Sawatzki G (1991) Influence of lactoferrin on the function of human polymorphonuclear leukocytes and monocytes. J Leukoc Biol 49:427–433

    CAS  PubMed  Google Scholar 

  • Gifford JL, Hunter HN, Vogel HJ (2005) Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell Mol Life Sci 62:2588–2598

    Article  CAS  PubMed  Google Scholar 

  • Grey A, Banovic T, Zhu Q, Watson M, Callon K, Palmano K, Ross J, Naot D, Reid IR, Cornish J (2004) The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Mol Endocrinol 18:2268–2278

    Article  CAS  PubMed  Google Scholar 

  • Griffiths CE, Cumberbatch M, Tucker SC, Dearman RJ, Andrew S, Headon DR, Kimber I (2001) Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans. Br J Dermatol 144:715–725

    Article  CAS  PubMed  Google Scholar 

  • Groot F, Geijtenbeek TB, Sanders RW, Baldwin CE, Sanchez-Hernandez M, Floris R, van Kooyk Y, de Jong EC, Berkhout B (2005) Lactoferrin prevents dendritic cell-mediated immunodeficiency virus type 1 transmission by blocking the DC-SIGN–gp120 interaction. J Virol 79:3009–3015

    Article  CAS  PubMed  Google Scholar 

  • Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13:85–94

    Article  CAS  PubMed  Google Scholar 

  • Guillen C, McInnes IB, Vaughan DM, Kommajosyula S, Van Berkel PH, Leung BP, Aguila A, Brock JH (2002) Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice. J Immunol 168:3950–3957

    CAS  PubMed  Google Scholar 

  • Haversen L, Ohlsson BG, Hahn-Zoric M, Hanson LA, Mattsby-Baltzer I (2002) Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kappa B. Cell Immunol 220:83–95

    Article  CAS  PubMed  Google Scholar 

  • He SH, Xie H (2004) Modulation of histamine release from human colon mast cells by protease inhibitors. World J Gastroenterol 10:337–341

    CAS  PubMed  Google Scholar 

  • He S, McEuen AR, Blewett SA, Li P, Buckley MG, Leufkens P, Walls AF (2003) The inhibition of mast cell activation by neutrophil lactoferrin: uptake by mast cells and interaction with tryptase, chymase and cathepsin G. Biochem Pharmacol 65:1007–1015

    Article  CAS  PubMed  Google Scholar 

  • Hwang SA, Kruzel ML, Actor JK (2005) Lactoferrin augments BCG vaccine efficacy to generate T helper response and subsequent protection against challenge with virulent Mycobacterium tuberculosis. Int Immunopharmacol 5:591–599

    Article  CAS  PubMed  Google Scholar 

  • Hwang SA, Kruzel ML, Actor JK (2008) Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages. Biochimie 91:76–85

    Article  PubMed  Google Scholar 

  • Ishii K, Takamura N, Shinohara M, Wakui N, Shin H, Sumino Y, Ohmoto Y, Teraguchi S, Yamauchi K (2003) Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. Hepatol Res 25:226–233

    Article  CAS  PubMed  Google Scholar 

  • Jenssen H, Hancock RE (2009) Antimicrobial properties of lactoferrin. Biochimie 91:19–29

    Article  CAS  PubMed  Google Scholar 

  • Jerala R (2007) Structural biology of the LPS recognition. Int J Med Microbiol 297:353–363

    Article  CAS  PubMed  Google Scholar 

  • Kai K, Komine K, Komine Y, Kuroishi T, Kozutsumi T, Kobayashi J, Ohta M, Kitamura H, Kumagai K (2002) Lactoferrin stimulates A Staphylococcus aureus killing activity of bovine phagocytes in the mammary gland. Microbiol Immunol 46:187–194

    CAS  PubMed  Google Scholar 

  • Kijlstra A, Jeurissen SH (1982) Modulation of classical C3 convertase of complement by tear lactoferrin. Immunology 47:263–270

    CAS  PubMed  Google Scholar 

  • Kimber I, Cumberbatch M, Dearman RJ, Headon DR, Bhushan M, Griffiths CE (2002) Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation. Biochem Cell Biol 80:103–107

    Article  CAS  PubMed  Google Scholar 

  • Kruzel ML, Harari Y, Mailman D, Actor JK, Zimecki M (2002) Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice. Clin Exp Immunol 130:25–31

    Article  CAS  PubMed  Google Scholar 

  • Kruzel ML, Bacsi A, Choudhury B, Sur S, Boldogh I (2006) Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 119:159–166

    Article  CAS  PubMed  Google Scholar 

  • Kuhara T, Iigo M, Itoh T, Ushida Y, Sekine K, Terada N, Okamura H, Tsuda H (2000) Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutr Cancer 38:192–199

    Article  CAS  PubMed  Google Scholar 

  • Legrand D, van Berkel PH, Salmon V, van Veen HA, Slomianny MC, Nuijens JH, Spik G (1997) The N-terminal Arg2, Arg3 and Arg4 of human lactoferrin interact with sulphated molecules but not with the receptor present on Jurkat human lymphoblastic T-cells. Biochem J 327:841–846

    CAS  PubMed  Google Scholar 

  • Legrand D, Elass E, Pierce A, Mazurier J (2004a) Lactoferrin and host defence: an overview of its immuno-modulating and anti-inflammatory properties. Biometals 17:225–229

    Article  CAS  PubMed  Google Scholar 

  • Legrand D, Vigie K, Said EA, Elass E, Masson M, Slomianny MC, Carpentier M, Briand JP, Mazurier J, Hovanessian AG (2004b) Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. Eur J Biochem 271:303–317

    Article  CAS  PubMed  Google Scholar 

  • Legrand D, Elass E, Carpentier M, Mazurier J (2005) Lactoferrin: a modulator of immune and inflammatory responses. Cell Mol Life Sci 62:2549–2559

    Article  CAS  PubMed  Google Scholar 

  • Legrand D, Elass E, Carpentier M, Mazurier J (2006) Interactions of lactoferrin with cells involved in immune function. Biochem Cell Biol 84:282–290

    Article  CAS  PubMed  Google Scholar 

  • Legrand D, Pierce A, Elass E, Carpentier M, Mariller C, Mazurier J (2008) Lactoferrin structure and functions. Adv Exp Med Biol 606:163–194

    Article  PubMed  Google Scholar 

  • Mann DM, Romm E, Migliorini M (1994) Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin. J Biol Chem 269:23661–23667

    CAS  PubMed  Google Scholar 

  • Mattsby-Baltzer I, Roseanu A, Motas C, Elverfors J, Engberg I, Hanson LA (1996) Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells. Pediatr Res 40:257–262

    Article  CAS  PubMed  Google Scholar 

  • Mazurier J, Legrand D, Hu WL, Montreuil J, Spik G (1989) Expression of human lactotransferrin receptors in phytohemagglutinin-stimulated human peripheral blood lymphocytes. Isolation of the receptors by antiligand-affinity chromatography. Eur J Biochem 179:481–487

    Article  CAS  PubMed  Google Scholar 

  • McAleer JP, Vella AT (2008) Understanding how lipopolysaccharide impacts CD4 T-cell immunity. Crit Rev Immunol 28:281–299

    CAS  PubMed  Google Scholar 

  • Meilinger M, Haumer M, Szakmary KA, Steinbock F, Scheiber B, Goldenberg H, Huettinger M (1995) Removal of lactoferrin from plasma is mediated by binding to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor and transport to endosomes. FEBS Lett 360:70–74

    Article  CAS  PubMed  Google Scholar 

  • Miyauchi H, Hashimoto S, Nakajima M, Shinoda I, Fukuwatari Y, Hayasawa H (1998) Bovine lactoferrin stimulates the phagocytic activity of human neutrophils: identification of its active domain. Cell Immunol 187:34–37

    Article  CAS  PubMed  Google Scholar 

  • Miyazawa K, Mantel C, Lu L, Morrison DC, Broxmeyer HE (1991) Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells. J Immunol 146:723–729

    CAS  PubMed  Google Scholar 

  • Montreuil J, Tonnelat J, Mullet S (1960) Preparation and properties of lactosiderophilin (lactotransferrin) of human milk. Biochim Biophys Acta 45:413–421

    Article  CAS  PubMed  Google Scholar 

  • Mukaida N (2000) Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation. Int J Hematol 72:391–398

    CAS  PubMed  Google Scholar 

  • Mulder AM, Connellan PA, Oliver CJ, Morris CA, Stevenson LM (2008) Bovine lactoferrin supplementation supports immune and antioxidant status in healthy human males. Nutr Res 28:583–589

    Article  CAS  PubMed  Google Scholar 

  • Na YJ, Han SB, Kang JS, Yoon YD, Park SK, Kim HM, Yang KH, Joe CO (2004) Lactoferrin works as a new LPS-binding protein in inflammatory activation of macrophages. Int Immunopharmacol 4:1187–1199

    Article  CAS  PubMed  Google Scholar 

  • Oh SM, Hahm DH, Kim IH, Choi SY (2001) Human neutrophil lactoferrin trans-activates the matrix metalloproteinase 1 gene through stress-activated MAPK signaling modules. J Biol Chem 276:42575–42579

    Article  CAS  PubMed  Google Scholar 

  • Oh SM, Pyo CW, Kim Y, Choi SY (2004) Neutrophil lactoferrin upregulates the human p53 gene through induction of NF-kappaB activation cascade. Oncogene 23:8282–8291

    Article  CAS  PubMed  Google Scholar 

  • Puddu P, Carollo MG, Belardelli F, Valenti P, Gessani S (2007) Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages. J Leukoc Biol 82:347–353

    Article  CAS  PubMed  Google Scholar 

  • Puddu P, Valenti P, Gessani S (2009) Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie 91:11–18

    Article  CAS  PubMed  Google Scholar 

  • Rainard P (1993) Activation of the classical pathway of complement by binding of bovine lactoferrin to unencapsulated Streptococcus agalactiae. Immunology 79:648–652

    CAS  PubMed  Google Scholar 

  • Samuelsen O, Haukland HH, Ulvatne H, Vorland LH (2004) Anti-complement effects of lactoferrin-derived peptides. FEMS Immunol Med Microbiol 41:141–148

    Article  CAS  PubMed  Google Scholar 

  • Schwartz N (2000) Biosynthesis and regulation of expression of proteoglycans. Front Biosci 5:649–655

    Google Scholar 

  • Sfeir RM, Dubarry M, Boyaka PN, Rautureau M, Tome D (2004) The mode of oral bovine lactoferrin administration influences mucosal and systemic immune responses in mice. J Nutr 134:403–409

    CAS  PubMed  Google Scholar 

  • Shimamura M, Yamamoto Y, Ashino H, Oikawa T, Hazato T, Tsuda H, Iigo M (2004) Bovine lactoferrin inhibits tumor-induced angiogenesis. Int J Cancer 111:111–116

    Article  CAS  PubMed  Google Scholar 

  • Shinoda I, Takase M, Fukuwatari Y, Shimamura S, Koller M, Konig W (1996) Effects of lactoferrin and lactoferricin on the release of interleukin 8 from human polymorphonuclear leukocytes. Biosci Biotechnol Biochem 60:521–523

    Article  CAS  PubMed  Google Scholar 

  • Smith WB, Gamble JR, Clark-Lewis I, Vadas MA (1991) Interleukin-8 induces neutrophil transendothelial migration. Immunology 72:65–72

    CAS  PubMed  Google Scholar 

  • Sorimachi K, Akimoto K, Hattori Y, Ieiri T, Niwa A (1997) Activation of macrophages by lactoferrin: secretion of TNF-alpha, IL-8 and NO. Biochem Mol Biol Int 43:79–87

    CAS  PubMed  Google Scholar 

  • Spadaro M, Caorsi C, Ceruti P, Varadhachary A, Forni G, Pericle F, Giovarelli M (2008) Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells. FASEB J 22:2747–2757

    Article  CAS  PubMed  Google Scholar 

  • Suzuki YA, Lopez V, Lonnerdal B (2005) Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci 62:2560–2575

    Article  CAS  PubMed  Google Scholar 

  • Takakura N, Wakabayashi H, Ishibashi H, Yamauchi K, Teraguchi S, Tamura Y, Yamaguchi H, Abe S (2004) Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model. J Med Microbiol 53:495–500

    Article  CAS  PubMed  Google Scholar 

  • Taylor KR, Gallo RL (2006) Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation. FASEB J 20:9–22

    Article  CAS  PubMed  Google Scholar 

  • van Berkel PH, Geerts ME, van Veen HA, Mericskay M, de Boer HA, Nuijens JH (1997) N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. Biochem J 328:145–151

    PubMed  Google Scholar 

  • Wakabayashi H, Takakura N, Teraguchi S, Tamura Y (2003) Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Microbiol Immunol 47:37–43

    CAS  PubMed  Google Scholar 

  • Wakabayashi H, Kurokawa M, Shin K, Teraguchi S, Tamura Y, Shiraki K (2004) Oral lactoferrin prevents body weight loss and increases cytokine responses during herpes simplex virus type 1 infection of mice. Biosci Biotechnol Biochem 68:537–544

    Article  CAS  PubMed  Google Scholar 

  • Ward PP, Mendoza-Meneses M, Park PW, Conneely OM (2008) Stimulus-dependent impairment of the neutrophil oxidative burst response in lactoferrin-deficient mice. Am J Pathol 172:1019–1029

    Article  CAS  PubMed  Google Scholar 

  • Yamauchi K, Wakabayashi H, Shin K, Takase M (2006) Bovine lactoferrin: benefits and mechanism of action against infections. Biochem Cell Biol 84:291–296

    Article  CAS  PubMed  Google Scholar 

  • Zagulski T, Lipinski P, Zagulska A, Broniek S, Jarzabek Z (1989) Lactoferrin can protect mice against a lethal dose of Escherichia coli in experimental infection in vivo. Br J Exp Pathol 70:697–704

    CAS  PubMed  Google Scholar 

  • Ziere GJ, Kruijt JK, Bijsterbosch MK, van Berkel TJ (1996) Recognition of lactoferrin and aminopeptidase M-modified lactoferrin by the liver: involvement of proteoglycans and the remnant receptor. Biochem J 313:289–295

    CAS  PubMed  Google Scholar 

  • Zimecki M, Mazurier J, Machnicki M, Wieczorek Z, Montreuil J, Spik G (1991) Immunostimulatory activity of lactotransferrin and maturation of CD4-CD8- murine thymocytes. Immunol Lett 30:119–123

    Article  CAS  PubMed  Google Scholar 

  • Zimecki M, Mazurier J, Spik G, Kapp JA (1995) Human lactoferrin induces phenotypic and functional changes in murine splenic B cells. Immunology 86:122–127

    CAS  PubMed  Google Scholar 

  • Zimecki M, Kocieba M, Kruzel M (2002) Immunoregulatory activities of lactoferrin in the delayed type hypersensitivity in mice are mediated by a receptor with affinity to mannose. Immunobiology 205:120–131

    Article  CAS  PubMed  Google Scholar 

  • Zweiman B, Kucich U, Shalit M, Von Allmen C, Moskovitz A, Weinbaum G, Atkins PC (1990) Release of lactoferrin and elastase in human allergic skin reactions. J Immunol 144:3953–3960

    CAS  PubMed  Google Scholar 

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Legrand, D., Mazurier, J. A critical review of the roles of host lactoferrin in immunity. Biometals 23, 365–376 (2010). https://doi.org/10.1007/s10534-010-9297-1

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