Cited by 141Neutrophil, Myeloperoxidase and Oxidative MechanismsImmune Response and Inflammationinterferon and immune responses

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Human neutrophils produce interferon gamma upon stimulation by interleukin-12

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Ethuin, Frédéric, Gérard, Bénédicte, Benna, Jamel E, Boutten, Anne, Gougereot-Pocidalo, Marie-Anne, Jacob, Laurent, Chollet-Martin, Sylvie·2004·Laboratory Investigation

DOI 10.1038/labinvest.3700148

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Abstract

Interferon gamma (IFNgamma) is a Th1 cytokine mainly produced by T cells, NK cells and macrophages in response to interleukin (IL)-12. As polymorphonuclear neutrophils (PMN) have been shown to produce and to release numerous cytokines, in particular upon IL-12 stimulation, we investigated the ability of highly purified PMN to secrete IFNgamma. We found that PMN contained a small store of IFNgamma, and that this store was rapidly secreted upon stimulation by degranulating agents such as formyl peptides. Moreover, after a few hours of stimulation with appropriate agents, PMN synthesized IFNgamma. The effect of IL-12 was time- and concentration-dependent, and IL-12 combinations with IL-2, IL-15, IL-18 or LPS were highly synergistic. Cycloheximide inhibited IFNgamma release in such optimal conditions, confirming the ability of PMN to synthesize IFNgamma. IFNgamma synthesis was associated with an increase in specific mRNA content, pointing to a transcriptional mechanism. The IFNgamma produced by PMN was biologically active, as demonstrated by its ability to induce TNFalpha synthesis by PMN themselves or to induce IL-10 synthesis by peripheral blood mononuclear cells. These findings reveal a novel pathway of autocrine and paracrine PMN activation. They also identified a new role for IFNgamma, bridging innate and adaptive immune responses.

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Authors: Ethuin, F., Gérard, B., Benna, J. E., Boutten, A., Gougereot-Pocidalo, M.-A., Jacob, L., & Chollet-Martin, S.
Affiliations: Inserm (FR)
Hôpital Bichat-Claude-Bernard (FR)
Hôpital Saint-Louis (FR)
ORCID: Gérard, Bénédicte
Benna, Jamel E
Boutten, Anne
Jacob, Laurent
Venue: Laboratory Investigation
Publisher: Elsevier BV
Published: 2004-10
Volume: 84
Issue: 10
Pages: 1363-1371
ISSN: 0023-6837 (ISSN-L)
DOI: 10.1038/labinvest.3700148
OpenAlex: W2014770545
Cited by: 141
References: 49
Citations by year: 2026: 4 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 6 · 2013: 11 · 2012: 11
FWCI: 1.80
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6676 d)
Locations: Laboratory Investigation (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords: interferon-gamma, neutrophils, IL-12, cytokine production, degranulation, formyl peptides, cytokine synergy, IL-15, IL-18, lipopolysaccharide, autocrine activation, innate-adaptive immune bridge, TNF-alpha induction, transcriptional regulation
MeSH terms: Adjuvants, Immunologic, Cell Separation, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Interferon-gamma, Lipopolysaccharides, Lymphocyte Activation, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, RNA, Messenger, Blotting, Western, Cell Degranulation, Interleukin-12, Interleukin-15, Reverse Transcriptase Polymerase Chain Reaction

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Human neutrophils produce interferon gamma upon stimulation by interleukin-12

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