A Bactericidal Effect for Human Lactoferrin

Arnold, Roland R.; Cole, Michael F.; McGhee, Jerry R.

doi:10.1126/science.327545

Cited by 618 publications

(297 citation statements)

References 20 publications

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“…Thus, lactoferrin exerts antiviral effects by binding directly to DNA (or RNA) and by preventing the entry of viruses into cells, thereby stopping infections at an early stage [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a combined chemical and computational study

et al. 2014

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Abstract.Three forms of lactoferrin (Lf) that differed in their levels of iron loading (Lf, LfFe, and LfFe 2 ) were simultaneously labeled with the fluorophores AF350 and AF430. All three resulting fluorescent lactoferrins exhibited fluorescence resonance energy transfer (FRET), but they all presented different FRET patterns. Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET was seen for the holo form (LfFe 2 ). For each form of metal-loaded lactoferrin, the AF350-AF430 distance varied depending on the protein conformation, which in turn depended on the level of iron loading. Thus, the FRET patterns of these lactoferrins were found to correlate with their iron loading levels. In order to gain greater insight into the number of fluorophores and the different FRET patterns observed (i.e., their iron levels), a computational analysis was performed. The results highlighted a number of lysines that have the greatest influence on the FRET profile. Moreover, despite the lack of an X-ray structure for any LfFe species, our study also showed that this species presents modified subdomain organization of the N-lobe, which narrows its iron-binding site. Complete domain rearrangement occurs during the LfFe to LfFe 2 transition. This latter study demonstrated that lactoferrin supplies iron to this bacterium, and suggested that this process occurs with no protein internalization.

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Section: Introductionmentioning

confidence: 99%

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a combined chemical and computational study

et al. 2014

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“…Similarly, transferrin contributes to antibody-and complementmediated serum antibacterial activity towards several Gram-negative species, although the mechanism of action is not known (Bullen et al, 1978;Griffiths, 1975;Norrod & Williams, 1978;Fitzgerald & Rogers, 1980). Finally, other work indicates that lactoferrin may directly kill selected bacterial strains through an undefined mechanism (Arnold et al, 1977(Arnold et al, , 1982Bortner et al, 1986;Kalmar & Arnold, 1988).…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+

Ellison¹,

LaForce²,

Giehl³

et al. 1990

Journal of General Microbiology

109

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Lactoferrin and transferrin have antimicrobial activity against selected Gram-negative bacteria, but the mechanism of action has not been defined. We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane. Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+. Addition of Ca2+ also blocked the ability of lactofenin to increase the susceptibility of Escherichia coli to rifampicin. Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+. In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin. These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+.

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“…It is present in high concentrations in human milk and in lower concentrations in a variety of secretions derived from glandular epithelium cells such as the prostate and salivary glands (2). LF also is found in high concentrations in the secondary granules of neutrophils (3,4). The primary functions of LF appear to be iron transport, storage, and chelation.…”

mentioning

confidence: 99%

“…This latter function is thought to be responsible for the bacteriostatic activity of LF. Free iron required for bacterial growth is depleted when neutrophilic granulocytes release LF (3).…”

mentioning

confidence: 99%

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

Siebert

Huang

1997

Proc. Natl. Acad. Sci. U.S.A.

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Lactoferrin (LF), traditionally known as an iron-binding protein present in high concentrations in milk and various secretions, has emerged as a multifunctional protein involved in many aspects of the host defense against infection. Recently, LF has been shown to inhibit the growth of solid tumors and reduce experimental metastasis in mice, suggesting that LF also may play a role in the defense against tumorigenesis. Here we provide the sequence of the cDNA and promoter region, the chromosome assignment, and tissue expression pattern of a novel form of LF mRNA (⌬LF). The sequence of ⌬LF mRNA is nearly identical to that of LF mRNA; however, at the 5 end, we find a novel sequence that replaces the N-terminal signal peptide sequence of LF mRNA. We map the ⌬LF mRNA to human chromosome 3 and find that both ⌬LF and LF sequences colocalize to the same cloned 90-to 150-kb genomic DNA fragment. We further show that the ⌬LF mRNA is the product of alternative splicing of the LF gene and likely is specified by use of an alternative promoter. Although we find ⌬LF mRNA at various levels in 20 of 20 adult and fetal human tissues, we do not find ⌬LF mRNA in any of 14 diverse tumor-derived cell lines.

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A Bactericidal Effect for Human Lactoferrin

Cited by 618 publications

References 20 publications

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a combined chemical and computational study

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a combined chemical and computational study

Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

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