The Journal of Experimental Medicine
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Published online 27 January 2003 doi:10.1084/jem.20021343
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© Rockefeller University Press, 0022-1007/2003/2/297 $5.00
The Journal of Experimental Medicine, Volume 197, Number 3, 297-302

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

Patrizia Scapini1, Bernardetta Nardelli3, Gianpaolo Nadali2, Federica Calzetti1, Giovanni Pizzolo2, Cesare Montecucco4 and Marco A. Cassatella1

1 Department of Pathology, University of Verona, 37134 Verona, Italy
2 Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
3 Human Genome Sciences, Inc., Rockville, MD 20850
4 Department of Experimental Medicine, University of Padova, 35121 Padova, 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: marco.cassatella{at}univr.it

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, IFN{gamma}, 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.

Key Words: IFN{gamma} • inflammation • B lymphocytes • monocytes • dendritic cells


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