Identification of the bactericidal domain of lactoferrin

Bellamy, Wayne; Takase, Mitsunori; Yamauchi, Koji; Wakabayashi, Hiroyuki; Kawase, Kouzou; Tomita, Mamoru

doi:10.1016/0167-4838(92)90346-f

Cited by 826 publications

(641 citation statements)

References 30 publications

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“…The ferrochelating properties of LF also result in antimicrobial activity of LF in human plasma serum, as iron deprivation inhibits bacterial growth (Aguila et al, 2001). Additionally, LF exerts bactericidal activity against antibiotic-resistant bacteria in vitro independent of its iron-binding capacity (Bellamy et al, 1992;Nibbering et al, 2001). These findings indicate that LF may protect against indomethacin-induced enteropathy by preventing intrusion of bacteria in the epithelium of the small intestine, which occurs when the intestinal epithelium becomes more permeable and results in a further progression of the damage.…”

Section: Discussionmentioning

confidence: 99%

“…Bactericidal (Bellamy et al, 1992;Zagulski et al, 1998), anti-inflammatory (Nuijens et al, 1996), antiviral (Swart et al, 1998;Ikeda et al, 2000;Murphy et al, 2000) and antioxidative activities (Gutteridge et al, 1981;Baldwin et al, 1984;Davidson & Lonnerdal, 1989) were discovered previously. Concomitant ingestion of lactoferrin together with indomethacin may protect against indomethacin-induced gastroenteropathy.…”

Section: Introductionmentioning

confidence: 98%

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Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. Design: A randomized crossover dietary intervention. Subjects and interventions: In all, 15 healthy volunteers (age 2371.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time ¼ À24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t ¼ À9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t ¼ À1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t ¼ 0, a permeability test was performed. Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio ¼ 0.036; 0.014-0.092, Po0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P ¼ 0.3). Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. Sponshorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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“…Lactoferrin is an iron-binding protein present in several secretions such as tears, saliva and synovial fluid and has broad antibacterial and physiological properties in addition to its antiviral activity (Bellamy et al 1992;Shimazaki 2000;van der Strate et al 2001). The concentrations of lactoferrin range from 0AE02 to 0AE2 mg ml )1 in bovine milk to 2 mg ml )1 in human milk (Shimazaki 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The concentrations of lactoferrin range from 0AE02 to 0AE2 mg ml )1 in bovine milk to 2 mg ml )1 in human milk (Shimazaki 2000). In addition, Bellamy et al (1992) isolated and sequenced the antibacterial peptides, lactoferricin H from a digest of human lactoferrin (residues 1-47) and lactoferricin B from a digest of bovine lactoferrin (residues 17-41), with both peptides being derived from the N-terminal domain of the respective lactoferrin molecules. Bioactive milk proteins and their derivative peptides with antiviral properties may, in appropriate formulations, form the basis for alternative therapies for the prevention or treatment of viral infection in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

et al. 2003

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Aims:To characterize the effect of bovine lactoferrin and lactoferricin B against feline calicivirus (FCV), a norovirus surrogate and poliovirus (PV), as models for enteric viruses. Methods and Results: Crandell-Reese feline kidney (CRFK) cells were used for the propagation of FCV and monkey embryo kidney (MEK) cells for PV. The assays included visual assessment of cell lines for cytopathic effects and determination of the percentage cell death using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] dye reduction assay. Incubation of bovine lactoferrin with CRFK cells either prior to or together with FCV inoculation substantially reduced FCV infection. In contrast, the interference of lactoferrin with the infection of cells with PV was demonstrated only when lactoferrin was present with cell lines and virus for the entire assay period. Using indirect immunofluorescence, lactoferrin was detected on the surface of both CRFK and MEK cells, suggesting that the interference of viral infection may be attributed to lactoferrin binding to the surfaces of susceptible cells, thereby preventing the attachment of the virus particles. Lactoferricin B, a cationic antimicrobial peptide derived from the N-terminal domain of bovine lactoferrin, reduced FCV but not PV infection. Conclusion: Lactoferrin was shown to interfere with the infection of cells for both FCV and PV. However, lactoferricin B showed no interference of infection with PV and interference with infection for FCV required the presence of lactoferricin B together with the cell line and virus. Significance and Impact of the Study: An in vitro basis is provided for the effects of bovine lactoferrin and lactoferricin B in moderating food-borne infections of enteric viruses.

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“…32,33 An isolated N-terminal cationic peptide of LF (lactoferrin) has been shown to exhibit increased potency of bactericidal activity relative to the intact protein, with efficacy against a wide range of microorganisms including Gram-negative and Gram-positive bacteria. 34 It has also been speculated that LF indirectly contributes to the innate immune response of the neutrophil. Various reports indicate that LF may influence neutrophil recruitment to sites of infection by altering aggregation, adhesion, attachment, and/or motility of this cell type.…”

mentioning

confidence: 99%

Stimulus-Dependent Impairment of the Neutrophil Oxidative Burst Response in Lactoferrin-Deficient Mice

Ward

Mendoza-Meneses

Park

et al. 2008

The American Journal of Pathology

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Lactoferrin (LF) is an iron-binding protein found in milk, mucosal secretions, and the secondary granules of neutrophils in which it is considered to be an important factor in the innate immune response against microbial infections. Moreover, LF deficiency in the secondary granules of neutrophils has long been speculated to contribute directly to the hypersusceptibility of specific granule deficiency (SGD) patients to severe, life-threatening bacterial infections. However, the exact physiological significance of LF in neutrophil-mediated host defense mechanisms remains controversial and has not yet been clearly established in vivo using relevant animal models. In this study, we used lactoferrin knockout (LFKO) mice to directly address the selective role of LF in the host defense response of neutrophils and to determine its contribution, if any, to the phenotype of SGD. Neutrophil maturation, migration, phagocytosis, granule release, and antimicrobial response to bacterial challenge were unaffected in LFKO mice. Interestingly, a stimulus-dependent defect in the oxidative burst response of LFKO neutrophils was observed in that normal activation was seen in response to opsonized bacteria whereas an impaired response was evident after phorbol myristate-13-acetate stimulation. Taken together, these results indicate that although LF deficiency alone is not a primary cause of the defects associated with SGD, this protein does play an immunomodulatory role in the oxidative burst response of neutrophils.

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Identification of the bactericidal domain of lactoferrin

Cited by 826 publications

References 30 publications

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

Stimulus-Dependent Impairment of the Neutrophil Oxidative Burst Response in Lactoferrin-Deficient Mice

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