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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon its degree of iron saturation. In addition, this study suggests a potential role for PMN in host defense against L. pneumophila--providing apolactoferrin to infected monocytes--and it supports the concept that PMN and monocytes may cooperate in host defense against intracellular parasites and other pathogens.
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PMID:Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. 191 66

Lactoferrin has been previously shown to be bactericidal for Legionella pneumophila. The current study showed that CaCl2, Mg(NO3)2, and MgCl2, but not NaCl, blocked killing. Activity was pH dependent with the greatest activity at 5.0. Sensitivity of the organism was dramatically affected by the growth conditions. Log phase 12 h, broth-grown cells were most sensitive, with older cultures becoming more resistant. Plate-grown cells were completely resistant. Lactoferrin binding, as detected by immunofluorescence microscopy, was temperature dependent (no binding at 4 degrees C), but was independent of killing.
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PMID:Bactericidal effect of lactoferrin on Legionella pneumophila: effect of the physiological state of the organism. 269 99

Lactoferrin, an iron-binding protein found in mucosal secretions and in specific granules of polymorphonuclear leukocytes, has been shown to be bactericidal for a variety of organisms. In this study, the effect of lactoferrin on Legionella pneumophila was investigated. Purified human apolactoferrin was bactericidal for the Knoxville 1 strain (serogroup 1), with a 4-log decrease in viability within 2 h at 37 degrees C. Killing was dependent on the iron-free state since iron-saturated lactoferrin had no activity. Guinea pig passage of this strain did not affect its sensitivity to lactoferrin. Treatment of the cells with dilutions of the lactoferrin resulted in correspondingly reduced killing. Activity was temperature dependent; there was no loss of viability at 1 or 22 degrees C and slightly enhanced killing at 41 degrees C. Addition of Mg2+ blocked bactericidal activity. In addition, mature human milk, a lactoferrin-containing mucosal secretion, was also bactericidal for L. pneumophila. As demonstrated with the purified lactoferrin, bactericidal activity was lost when the milk was iron saturated.
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PMID:Bactericidal effect of lactoferrin on Legionella pneumophila. 394 91

The action of bovine lactoferrin saturated with iron, zinc and manganese on the intracellular multiplication of Legionella pneumophila in HeLa cells has been tested. The results obtained showed that lactoferrin did not influence the invasive efficiency of Legionella. The intracellular multiplication of the bacterium was inhibited by apo-lactoferrin and by lactoferrin saturated with manganese and zinc, whereas lactoferrin saturated with iron enhanced the intracellular growth. Experiments in parallel were performed with iron, manganese and zinc citrate to test the effect due to the metal ions alone. Even in this condition the addition of an iron chelate enhanced the multiplication of Legionella while the manganese chelate produced a certain inhibition.
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PMID:Metal complexes of lactoferrin and their effect on the intracellular multiplication of Legionella pneumophila. 1083 Dec 20

Lactoferrin (Lf) is a multifunctional iron glycoprotein which is known to exert a broad-spectrum primary defense activity against bacteria, fungi, protozoa and viruses. Its iron sequestering property is at the basis of the bacteriostatic effect, which can be counteracted by bacterial pathogens by two mechanisms: the production of siderophores which bind ferric ion with high affinity and transport it into cells, or the expression of specific receptors capable of removing the iron directly from lactoferrin at the bacterial surface. A particular aspect of the problem of iron supply occurs in bacteria (e.g. Legionella) which behave as intracellular pathogens, multiplying in professional and non professional macrophages of the host. Besides this bacteriostatic action, Lf can show a direct bactericidal activity due to its binding to the lipid A part of bacterial LPS, with an associated increase in membrane permeability. This action is due to lactoferricin (Lfc), a peptide obtained from Lf by enzymatic cleavage, which is active not only against bacteria, but even against fungi, protozoa and viruses. Additional antibacterial activities of Lf have also been described. They concern specific effects on the biofilm development, the bacterial adhesion and colonization, the intracellular invasion, the apoptosis of infected cells and the bactericidal activity of PMN. The antifungal activity of Lf and Lfc has been mainly studied towards Candida, with direct action on Candida cell membranes. Even the sensitivity of the genus tricophyton has been studied, indicating a potential usefulness of this molecule. Among protozoa, Toxoplasma gondii is sensitive to Lf, both in vitro and in vivo tests, while Trichomonads can use lactoferrin for iron requirements. As to the antiviral activity, it is exerted against several enveloped and naked viruses, with an inhibition which takes place in the early phases of viral invection, as a consequence of binding to the viral particle or to the cell receptors for virus. The antiviral activity of Lf has also been demonstrated in in vivo model invections and proposed for a selective delivery of antiviral drugs. The new perspectives in the studies on the antimicrobial activity of Lf appear to be linked to its potential prophylactic and therapeutical use in a considerable spectrum of medical conditions, taking advantage of the availability of the recombinant human Lf. But the historical evolution of our knowledge on Lf indicates that its antimicrobial activity must be considered in a general picture of all the biological properties of this multifunctional protein.
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PMID:The antimicrobial activity of lactoferrin: current status and perspectives. 1522 64