IFNα-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells

Cristina Tecchio, Veronica Huber, Patrizia Scapini, Federica Calzetti, Daniela Margotto, Giuseppe Todeschini, Lorenzo Pilla, Giovanni Martinelli, Giovanni Pizzolo, Licia Rivoltini, Marco A. Cassatella

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-related apoptosis-Inducing ligand (TRAIL) is a member of the TNF superfamily exerting cytotoxic activities toward tumor cells. Herein, we demonstrate that therapeutic concentrations of interferon α (IFNα) stimulate the expression of high levels of TRAIL mRNA and the release of elevated amounts of a soluble bioactive form of TRAIL (sTRAIL) in both human neutrophils and monocytes. Supernatants harvested from IFNα-treated neutrophils/monocytes elicited, on TRAIL-sensitive leukemic cell lines, proapoptotic activities that were significantly reduced by either a combination of TRAIL-R1/Fc and TRAIL-R2/Fc chimeras or neutralizing anti-TRAIL, anti-TRAIL-R1, and anti-TRAIL-R2 antibodies, suggesting that they were mediated by released sTRAIL acting on both TRAIL receptors. Since diseases such as chronic myeloid leukemia (CML) and melanoma are effectively treated with IFNα, we also demonstrate that CML neutrophils and peripheral blood mononuclear cells (PBMCs) cultured with IFNα at therapeutic concentrations retain the capacity of releasing sTRAIL, suggesting that CML leukocytes, in vivo, might represent an Important source of sTRAIL. In this regard, we show that sTRAIL serum levels as well as leukocyte-associated TRAIL significantly increase in melanoma patients following IFNO administration. Collectively, these findings indicate that sTRAIL released by IFNα-activated neutrophils and monocytes contributes not only to the immunoregulatory actions but also to the therapeutic activities of IFNα.

Original languageEnglish
Pages (from-to)3837-3844
Number of pages8
JournalBlood
Volume103
Issue number10
DOIs
Publication statusPublished - May 15 2004

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TNF-Related Apoptosis-Inducing Ligand
Cell death
Interferons
Monocytes
Neutrophils
Tumor Necrosis Factor-alpha
Ligands
Apoptosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Melanoma
Leukocytes
Cells
TNF-Related Apoptosis-Inducing Ligand Receptors
Tumors
Blood Cells
Blood
Therapeutics

ASJC Scopus subject areas

  • Hematology

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IFNα-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. / Tecchio, Cristina; Huber, Veronica; Scapini, Patrizia; Calzetti, Federica; Margotto, Daniela; Todeschini, Giuseppe; Pilla, Lorenzo; Martinelli, Giovanni; Pizzolo, Giovanni; Rivoltini, Licia; Cassatella, Marco A.

In: Blood, Vol. 103, No. 10, 15.05.2004, p. 3837-3844.

Research output: Contribution to journalArticle

Tecchio, Cristina ; Huber, Veronica ; Scapini, Patrizia ; Calzetti, Federica ; Margotto, Daniela ; Todeschini, Giuseppe ; Pilla, Lorenzo ; Martinelli, Giovanni ; Pizzolo, Giovanni ; Rivoltini, Licia ; Cassatella, Marco A. / IFNα-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. In: Blood. 2004 ; Vol. 103, No. 10. pp. 3837-3844.
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AU - Scapini, Patrizia

AU - Calzetti, Federica

AU - Margotto, Daniela

AU - Todeschini, Giuseppe

AU - Pilla, Lorenzo

AU - Martinelli, Giovanni

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AU - Rivoltini, Licia

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