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    Lactoferrin: an important host defence against microbial and viral attack

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    Abstract. The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specifi c binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks

    Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin

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    Ovotransferrin (formerly conalbumin) is an iron-binding protein present in birds. It belongs to the transferrin family and shows about 50% sequence homology with mammalian serum transferrin and lactoferrin. This protein has been demonstrated to be capable of delivering iron to cells and of inhibiting bacterial multiplication. However, no antiviral activity has been reported for ovotransferrin, although the antiviral activity of human and bovine lactoferrins against several viruses, including human herpes simplex viruses, has been well established. In this report, the antiviral activity of ovotransferrin towards chicken embryo fibroblast infection by Marek's disease virus (MDV), an avian herpesvirus, was clearly demonstrated. Ovotransferrin was more effective than human and bovine lactoferrins in inhibiting MDV infection and no correlation between antiviral efficacy and iron saturation was found. The observations reported here are of interest from an evolutionary point of view since it is likely that the defensive properties of transferrins appeared early in evolution. In birds, the defensive properties of ovotransferrin remained joined to iron transport functions; in mammals, iron transport functions became peculiar to serum transferrin, and the defensive properties towards infections were optimised in lactoferri

    Effect of bovine lactoferricin on enteropathogenic Yersinia adhesion and invasion in HEp-2 cells

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    Bovine lactoferricin, a pepsin-generated antimicrobial peptide from bovine lactoferrin active against a wide range of bacteria, was tested for its ability to influence the adhesion and invasion of Yersinia enterocolitica and Yersinia pseudotuberculosis in HEp-2 cells. The addition of non-cytotoxic and non-bactericidal concentrations of lactoferricin to cell monolayers before infection, under different bacterial growth experimental conditions, was ineffective or resulted in about a 10-fold increase in bacterial adhesion, whereas, in bacteria grown in conditions allowing maximal inv gene expression, a 10-fold inhibition of cell invasion by lactoferricin was observed. To confirm that the anti-invasive activity of lactoferricin was exerted against invasin-mediated bacterial entry, experiments were also performed utilizing Escherichia coli strain HB101 (pRI203), harbouring the inv gene from Y. pseudotuberculosis, which allows penetration of mammalian cells. Under these experimental conditions, lactoferricin was able to inhibit bacterial entry into epithelial cells, demonstrating that this peptide acts on inv-mediated Yersinia species invasion. As the inv gene product is the most important virulence factor in enteropathogenic Yersinia, being responsible for bacterial adherence and penetration within epithelial cells of the intestinal lumen and for the subsequent colonization of regional lymph nodes, these data provide additional information on the protective role of lactoferricin against bacterial infection

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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