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Journal articles
Impaired efferocytosis and neutrophil extracellular traps clearance by macrophages in ARDS
Murielle Gregoire
1, 2
Fabrice Uhel
2, 1, 3
Mathieu Lesouhaitier
1, 3
Arnaud Gacouin
1, 3
Marion Guirriec
1, 2
Frederic Mourcin
1, 2
Erwan Dumontet
1, 2
Arnaud Chalin
4
Michel Samson
4
Laure-Line Berthelot
5
Adrien Tissot
5, 6
Mallorie Kerjouan
1
Stéphane Jouneau
4, 1
Yves Le Tulzo
2, 1, 3
Karin Tarte
1, 2
Jaroslaw W Zmijewski
7
Jean-Marc Tadié
2, 1, 3
Murielle Gregoire 1, 2
Author
Fabrice Uhel 2, 1, 3
Author
Mathieu Lesouhaitier 1, 3
Author
Arnaud Gacouin 1, 3
Author
Marion Guirriec 1, 2
Author
Frederic Mourcin 1, 2
Author
Erwan Dumontet 1, 2
Author
Arnaud Chalin 4
Author
Michel Samson 4
Author
Laure-Line Berthelot 5
Author
Adrien Tissot 5, 6
Author
Mallorie Kerjouan 1
Author
Stéphane Jouneau 4, 1
Author
Yves Le Tulzo 2, 1, 3
Author
Karin Tarte 1, 2
Author
Jaroslaw W Zmijewski 7
Author
Jean-Marc Tadié 2, 1, 3
Author
1
CHU Pontchaillou [Rennes] (2 Rue Henri le Guilloux, 35000 Rennes - France)
2
MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer (INSERM UMR1236, Campus Santé, Bât 2, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1236 (101, rue de Tolbiac, 75013 Paris - France)
- Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes (Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex - France)
3
CIC - Centre d'Investigation Clinique [Rennes] (Rue Henri Le Guilloux - Pavillon Clémenceau 35033 Rennes Cedex 9 - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- Hôpital Pontchaillou (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : CIC1414 (101, rue de Tolbiac, 75013 Paris - France)
4
Irset - Institut de recherche en santé, environnement et travail (263 avenue Général Leclerc 35042 Rennes Cedex - France)
- UA - Université d'Angers (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- EHESP - École des Hautes Études en Santé Publique [EHESP] (15, avenue du Pr. Léon Bernard - 35043 Rennes Cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1085 (101, rue de Tolbiac, 75013 Paris - France)
- Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes (Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex - France)
5
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie (CHU Nantes - Hôtel Dieu - 30 Bd Jean Monnet 44093 Nantes Cedex 01. - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1064 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
6
CHU Nantes - Centre hospitalier universitaire de Nantes (1 Place Alexis-Ricordeau, 44000 Nantes - France)
7
UAB - University of Alabama at Birmingham [ Birmingham] (1720 2nd Ave S, Birmingham, AL 35233 - United States)
Abstract : Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute to sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) and high-mobility group box 1 (HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing inflammation and ARDS severity.We investigated neutrophil and NET clearance by macrophages from control and ARDS patients and examined how bronchoalveolar lavage (BAL) fluid from control and ARDS patients could affect NET formation and efferocytosis. Metformin (an AMPK activator) and neutralising antibody against HMGB1 were applied to improve efferocytosis and NET clearance.Neutrophils from ARDS patients showed significantly reduced apoptosis. Conversely, NET formation was significantly enhanced in ARDS patients. Exposure of neutrophils to ARDS BAL fluid promoted NET production, while control BAL fluid had no effect. Macrophage engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients. Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL fluid improved efferocytosis and NET clearance.In conclusion, restoration of AMPK activity with metformin or specific neutralisation of HMGB1 in BAL fluid represent promising therapeutic strategies to decrease sustained lung inflammation during ARDS.
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Journal articles
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01833937
Contributor : Laurent Jonchère <>
Submitted on : Friday, September 14, 2018 - 1:18:53 PM
Last modification on : Sunday, January 5, 2020 - 11:28:02 AM
Document(s) archivé(s) le : Saturday, December 15, 2018 - 3:49:40 PM
Contributor : Laurent Jonchère <>
Submitted on : Friday, September 14, 2018 - 1:18:53 PM
Last modification on : Sunday, January 5, 2020 - 11:28:02 AM
Document(s) archivé(s) le : Saturday, December 15, 2018 - 3:49:40 PM
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Identifiers
- HAL Id : hal-01833937, version 1
- DOI : 10.1183/13993003.02590-2017
- PUBMED : 29946009
Collections
UNIV-RENNES1 | CRTI | MICMAC | IRSET-EHESP | IRSET-2 | IRSET-1 | BIOSIT | UR1-UFR-SVE | UNIV-RENNES | UNIV-NANTES | UNIV-ANGERS | CIC | CIC203 | IRSET | U917
Citation
Murielle Gregoire, Fabrice Uhel, Mathieu Lesouhaitier, Arnaud Gacouin, Marion Guirriec, et al.. Impaired efferocytosis and neutrophil extracellular traps clearance by macrophages in ARDS. European Respiratory Journal, European Respiratory Society, 2018, 52 (2), pp.1702590. ⟨10.1183/13993003.02590-2017⟩. ⟨hal-01833937⟩
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