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The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation

Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials...

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Autores principales: Majka, Grzegorz, Więcek, Grażyna, Śróttek, Małgorzata, Śpiewak, Klaudyna, Brindell, Małgorzata, Koziel, Joanna, Marcinkiewicz, Janusz, Strus, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116316/
https://www.ncbi.nlm.nih.gov/pubmed/27757565
http://dx.doi.org/10.1007/s10534-016-9973-x
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author Majka, Grzegorz
Więcek, Grażyna
Śróttek, Małgorzata
Śpiewak, Klaudyna
Brindell, Małgorzata
Koziel, Joanna
Marcinkiewicz, Janusz
Strus, Magdalena
author_facet Majka, Grzegorz
Więcek, Grażyna
Śróttek, Małgorzata
Śpiewak, Klaudyna
Brindell, Małgorzata
Koziel, Joanna
Marcinkiewicz, Janusz
Strus, Magdalena
author_sort Majka, Grzegorz
collection PubMed
description Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host’s health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis.
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spelling pubmed-51163162016-12-02 The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation Majka, Grzegorz Więcek, Grażyna Śróttek, Małgorzata Śpiewak, Klaudyna Brindell, Małgorzata Koziel, Joanna Marcinkiewicz, Janusz Strus, Magdalena Biometals Article Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host’s health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis. Springer Netherlands 2016-10-18 2016 /pmc/articles/PMC5116316/ /pubmed/27757565 http://dx.doi.org/10.1007/s10534-016-9973-x Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Majka, Grzegorz
Więcek, Grażyna
Śróttek, Małgorzata
Śpiewak, Klaudyna
Brindell, Małgorzata
Koziel, Joanna
Marcinkiewicz, Janusz
Strus, Magdalena
The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title_full The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title_fullStr The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title_full_unstemmed The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title_short The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
title_sort impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116316/
https://www.ncbi.nlm.nih.gov/pubmed/27757565
http://dx.doi.org/10.1007/s10534-016-9973-x
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