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G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS

B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNγ, express high levels of BLyS mRNA and release elevated amounts of biologic...

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Autores principales: Scapini, Patrizia, Nardelli, Bernardetta, Nadali, Gianpaolo, Calzetti, Federica, Pizzolo, Giovanni, Montecucco, Cesare, Cassatella, Marco A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193843/
https://www.ncbi.nlm.nih.gov/pubmed/12566413
http://dx.doi.org/10.1084/jem.20021343
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author Scapini, Patrizia
Nardelli, Bernardetta
Nadali, Gianpaolo
Calzetti, Federica
Pizzolo, Giovanni
Montecucco, Cesare
Cassatella, Marco A.
author_facet Scapini, Patrizia
Nardelli, Bernardetta
Nadali, Gianpaolo
Calzetti, Federica
Pizzolo, Giovanni
Montecucco, Cesare
Cassatella, Marco A.
author_sort Scapini, Patrizia
collection PubMed
description B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNγ, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSF–stimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by anti–G-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis.
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spelling pubmed-21938432008-04-11 G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS Scapini, Patrizia Nardelli, Bernardetta Nadali, Gianpaolo Calzetti, Federica Pizzolo, Giovanni Montecucco, Cesare Cassatella, Marco A. J Exp Med Article B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNγ, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSF–stimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by anti–G-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis. The Rockefeller University Press 2003-02-03 /pmc/articles/PMC2193843/ /pubmed/12566413 http://dx.doi.org/10.1084/jem.20021343 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Scapini, Patrizia
Nardelli, Bernardetta
Nadali, Gianpaolo
Calzetti, Federica
Pizzolo, Giovanni
Montecucco, Cesare
Cassatella, Marco A.
G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title_full G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title_fullStr G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title_full_unstemmed G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title_short G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
title_sort g-csf–stimulated neutrophils are a prominent source of functional blys
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193843/
https://www.ncbi.nlm.nih.gov/pubmed/12566413
http://dx.doi.org/10.1084/jem.20021343
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