G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils.

Autor:	Aymonnier K; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Bosetta E; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Leborgne NGF; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Ullmer A; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Le Gall M; Proteom'IC facility, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du Faubourg Saint Jacques, Paris F-75014, France., De Chiara A; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Salnot V; Proteom'IC facility, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du Faubourg Saint Jacques, Paris F-75014, France., Many S; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France., Scapini P; Department of General Pathology, University of Verona, Verona 37134, Italy., Wicks I; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.; Department of Rheumatology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia., Chatfield S; Department of Rheumatology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia., Martin KR; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia., Witko-Sarsat V; Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Jan 19; Vol. 115 (2), pp. 205-221.
DOI:	10.1093/jleuko/qiad122
Abstrakt:	Cytosolic proliferating cell nuclear antigen (PCNA) is involved in neutrophil survival and function, in which it acts as a scaffold and associates with proteins involved in apoptosis, NADPH oxidase activation, cytoskeletal dynamics, and metabolism. While the PCNA interactome has been characterized in neutrophils under homeostatic conditions, less is known about neutrophil PCNA in pathophysiological contexts. Granulocyte colony-stimulating factor (G-CSF) is a cytokine produced in response to inflammatory stimuli that regulates many aspects of neutrophil biology. Here, we used isolated normal-density neutrophils from G-CSF-treated haemopoietic stem cell donors (GDs) as a model to understand the role of PCNA during inflammation. Proteomic analysis of the neutrophil cytosol revealed significant differences between GDs and healthy donors (HDs). PCNA was one of the most upregulated proteins in GDs, and the PCNA interactome was significantly different in GDs compared with HDs. Importantly, while PCNA associated with almost all enzymes involved in glycolysis in HDs, these associations were decreased in GDs. Functionally, neutrophils from GDs had a significant increase in glycolysis compared with HDs. Using p21 competitor peptides, we showed that PCNA negatively regulates neutrophil glycolysis in HDs but had no effect on GD neutrophils. These data demonstrate that G-CSF alters the PCNA scaffold, affecting interactions with key glycolytic enzymes, and thus regulates glycolysis, the main energy pathway utilized by neutrophils. By this selective control of glycolysis, PCNA can organize neutrophils functionality in parallel with other PCNA mechanisms of prolonged survival. PCNA may therefore be instrumental in the reprogramming that neutrophils undergo in inflammatory or tumoral settings. Competing Interests: Conflict of interest statement. I.W. and K.R.M. have received funding from CSL Innovation Ltd for research on antagonists of haemopoietic growth factors. The authors declare that the research was conducted in the absence of any other commercial or financial relationships that could be construed as a potential conflict of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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