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HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity
In newborn the innate immune system provides essential protection during primary infections before the generation of an appropriate adaptive immune response that is initially not fully operative. Innate immune response is evoked and perpetuated by molecules derived from microorganisms or by the dama...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161821/ https://www.ncbi.nlm.nih.gov/pubmed/21915243 http://dx.doi.org/10.1371/journal.pone.0023766 |
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author | Ciucci, Alessandra Gabriele, Ida Percario, Zulema A. Affabris, Elisabetta Colizzi, Vittorio Mancino, Giorgio |
author_facet | Ciucci, Alessandra Gabriele, Ida Percario, Zulema A. Affabris, Elisabetta Colizzi, Vittorio Mancino, Giorgio |
author_sort | Ciucci, Alessandra |
collection | PubMed |
description | In newborn the innate immune system provides essential protection during primary infections before the generation of an appropriate adaptive immune response that is initially not fully operative. Innate immune response is evoked and perpetuated by molecules derived from microorganisms or by the damage/death of host cells. These are collectively known as damage-associated molecular-pattern (DAMP) molecules. High-mobility group box 1 protein (HMGB1) or amphoterin, which previously was considered to be only a nuclear factor, has been recently identified as a DAMP molecule. When it is actively secreted by inflammatory cells or passively released from necrotic cells, HMGB1 mediates the response to infection, injury and inflammation, inducing dendritic cells maturation and T helper-1-cell responses. To characterize the role of HMGB1 in the innate and immature defense mechanisms in newborns, human cord blood (CB) mononuclear cells, in comparison to adult peripheral blood (PB) mononuclear cells, have been analyzed for its expression. By flow cytometry and western blot analysis, we observed that in CB and PB cells: i) HMGB1 is expressed on cell surface membranes of myeloid dendritic cell precursors, mostly, and lymphocytes (gamma/delta and CD4(+) T cells) to a lesser extent; ii) different pro-inflammatory stimuli or molecules that mimic infection increased cell surface expression of HMGB1 as well as its secretion into extracellular environment; iii) the treatment with synthetic molecules such as aminobisphosphonates (ABs), identified to be γδ T cell antigens, triggered up-regulation of HMGB1 expression on mononuclear cells, as well γδ T lymphocytes, inducing its secretion. The modulation of its secretion and the HMGB1-mediated migration of monocytes indicated HMGB1 as regulator of immune response in an immature system, like CB, through engagement of γδ T lymphocytes and myeloid dendritic cell precursors, essential components of innate immunity. In addition, the increased HMGB1 expression/secretion triggered by ABs, previously characterized for their immuno-modulating and immune-adjuvant capabilities, indicated that immunomodulation might represent a new therapeutical approach for neonatal and adult pathologies. |
format | Online Article Text |
id | pubmed-3161821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31618212011-09-13 HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity Ciucci, Alessandra Gabriele, Ida Percario, Zulema A. Affabris, Elisabetta Colizzi, Vittorio Mancino, Giorgio PLoS One Research Article In newborn the innate immune system provides essential protection during primary infections before the generation of an appropriate adaptive immune response that is initially not fully operative. Innate immune response is evoked and perpetuated by molecules derived from microorganisms or by the damage/death of host cells. These are collectively known as damage-associated molecular-pattern (DAMP) molecules. High-mobility group box 1 protein (HMGB1) or amphoterin, which previously was considered to be only a nuclear factor, has been recently identified as a DAMP molecule. When it is actively secreted by inflammatory cells or passively released from necrotic cells, HMGB1 mediates the response to infection, injury and inflammation, inducing dendritic cells maturation and T helper-1-cell responses. To characterize the role of HMGB1 in the innate and immature defense mechanisms in newborns, human cord blood (CB) mononuclear cells, in comparison to adult peripheral blood (PB) mononuclear cells, have been analyzed for its expression. By flow cytometry and western blot analysis, we observed that in CB and PB cells: i) HMGB1 is expressed on cell surface membranes of myeloid dendritic cell precursors, mostly, and lymphocytes (gamma/delta and CD4(+) T cells) to a lesser extent; ii) different pro-inflammatory stimuli or molecules that mimic infection increased cell surface expression of HMGB1 as well as its secretion into extracellular environment; iii) the treatment with synthetic molecules such as aminobisphosphonates (ABs), identified to be γδ T cell antigens, triggered up-regulation of HMGB1 expression on mononuclear cells, as well γδ T lymphocytes, inducing its secretion. The modulation of its secretion and the HMGB1-mediated migration of monocytes indicated HMGB1 as regulator of immune response in an immature system, like CB, through engagement of γδ T lymphocytes and myeloid dendritic cell precursors, essential components of innate immunity. In addition, the increased HMGB1 expression/secretion triggered by ABs, previously characterized for their immuno-modulating and immune-adjuvant capabilities, indicated that immunomodulation might represent a new therapeutical approach for neonatal and adult pathologies. Public Library of Science 2011-08-22 /pmc/articles/PMC3161821/ /pubmed/21915243 http://dx.doi.org/10.1371/journal.pone.0023766 Text en Mancino et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ciucci, Alessandra Gabriele, Ida Percario, Zulema A. Affabris, Elisabetta Colizzi, Vittorio Mancino, Giorgio HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title | HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title_full | HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title_fullStr | HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title_full_unstemmed | HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title_short | HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity |
title_sort | hmgb1 and cord blood: its role as immuno-adjuvant factor in innate immunity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161821/ https://www.ncbi.nlm.nih.gov/pubmed/21915243 http://dx.doi.org/10.1371/journal.pone.0023766 |
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