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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3 February 2003
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January 27 2003
G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
Patrizia Scapini,
Patrizia Scapini
1Department of Pathology, University of Verona, 37134 Verona, Italy
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Bernardetta Nardelli,
Bernardetta Nardelli
3Human Genome Sciences, Inc., Rockville, MD 20850
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Gianpaolo Nadali,
Gianpaolo Nadali
2Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
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Federica Calzetti,
Federica Calzetti
1Department of Pathology, University of Verona, 37134 Verona, Italy
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Giovanni Pizzolo,
Giovanni Pizzolo
2Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
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Cesare Montecucco,
Cesare Montecucco
4Department of Experimental Medicine, University of Padova, 35121 Padova, Italy
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Marco A. Cassatella
Marco A. Cassatella
1Department of Pathology, University of Verona, 37134 Verona, Italy
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Patrizia Scapini
1Department of Pathology, University of Verona, 37134 Verona, Italy
Bernardetta Nardelli
3Human Genome Sciences, Inc., Rockville, MD 20850
Gianpaolo Nadali
2Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
Federica Calzetti
1Department of Pathology, University of Verona, 37134 Verona, Italy
Giovanni Pizzolo
2Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
Cesare Montecucco
4Department of Experimental Medicine, University of Padova, 35121 Padova, Italy
Marco A. Cassatella
1Department of Pathology, University of Verona, 37134 Verona, Italy
Address correspondence to Marco A. Cassatella, Dept. of Pathology, General Pathology Unit, Strada Le Grazie 4, 37134 Verona, Italy. Phone: 39-045-8027130; Fax: 39-045-8027127; E-mail: [email protected]
*
Abbreviations used in this paper: BLyS, B lymphocyte stimulator; HD, Hodgkin's; mono-DC, monocyte-derived dendritic cells.
Received:
August 05 2002
Revision Received:
October 18 2002
Accepted:
December 12 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (3): 297–302.
Article history
Received:
August 05 2002
Revision Received:
October 18 2002
Accepted:
December 12 2002
Citation
Patrizia Scapini, Bernardetta Nardelli, Gianpaolo Nadali, Federica Calzetti, Giovanni Pizzolo, Cesare Montecucco, Marco A. Cassatella; G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS . J Exp Med 3 February 2003; 197 (3): 297–302. doi: https://doi.org/10.1084/jem.20021343
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