Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Stephan Culemann; Katharina Knab; Maximilien Euler; Anja Wegner; Hilal Garibagaoglu; Jochen Ackermann; Kim Fischer; Deborah Kienhöfer; Georgiana Crainiciuc; Jonas Hahn; Anika Grüneboom; Falk Nimmerjahn; Stefan Uderhardt; Andrés Hidalgo; Georg Schett; Markus H. Hoffmann; Gerhard Krönke

doi:10.1084/jem.20220525

Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Stephan Culemann, Katharina Knab, Maximilien Euler, Anja Wegner, Hilal Garibagaoglu, Jochen Ackermann, Kim Fischer, Deborah Kienhöfer, Georgiana Crainiciuc, Jonas Hahn, Anika Grüneboom, Falk Nimmerjahn, Stefan Uderhardt, Andrés Hidalgo, Georg Schett, Markus H. Hoffmann, Gerhard Krönke^*

^*Corresponding author for this work

Department of Dermatology, Allergology and Venereology

64 Citations (Scopus)

Abstract

Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.

Original language	English
Article number	e20220525
Journal	Journal of Experimental Medicine
Volume	220
Issue number	6
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20220525
Publication status	Published - 05.06.2023

Funding

This work was supported by the Deutsche For-schungsgemeinschaft (FG 2886 “PANDORA” – B01/B02/A03/ B04 to G. Krönke, F. Nimmerjahn, G. Schett, and M.H. Hoffmann, respectively, and the CRC1181-A03/A01/A02/A07/C03 Z2 to G. Krönke, G. Schett, F. Nimmerjahn, and M.H. Hoffmann), the Emerging Field Initiative of the Friedrich-Alexander University Erlangen-Nürnberg (EFI_Verbund_Med_05_MIRACLE to G. Krönke), the Bundesministerium für Bildung und For-schung (MASCARA to G. Krönke and G. Schett; MelAutim to G. Krönke), and the European Union (Horizon 2020 ERC-2014-StG 640087 – SOS and ERC-2020-CoG 101001866 – INSPIRE to G. Krönke; and ERC-2018-SyG nanoSCOPE and RTCure to G. Schett). This work was supported by grants R01AI165661 from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, H2020-FET-OPEN-2018-2020 (no. 861878) from the European Commission to A. Hidalgo and M.H. Hoffmann, and HR17_00527 from Fundacion La Caixa to A. Hidalgo. The CNIC is supported by the Min-isterio de Ciencia e Innovacion and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award CEX2020-001041-S).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.21-05 Immunology

Access to Document

10.1084/jem.20220525

Cite this

Culemann, S., Knab, K., Euler, M., Wegner, A., Garibagaoglu, H., Ackermann, J., Fischer, K., Kienhöfer, D., Crainiciuc, G., Hahn, J., Grüneboom, A., Nimmerjahn, F., Uderhardt, S., Hidalgo, A., Schett, G., Hoffmann, M. H., & Krönke, G. (2023). Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes. Journal of Experimental Medicine, 220(6), Article e20220525. https://doi.org/10.1084/jem.20220525

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title = "Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes",

abstract = "Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.",

author = "Stephan Culemann and Katharina Knab and Maximilien Euler and Anja Wegner and Hilal Garibagaoglu and Jochen Ackermann and Kim Fischer and Deborah Kienh{\"o}fer and Georgiana Crainiciuc and Jonas Hahn and Anika Gr{\"u}neboom and Falk Nimmerjahn and Stefan Uderhardt and Andr{\'e}s Hidalgo and Georg Schett and Hoffmann, \{Markus H.\} and Gerhard Kr{\"o}nke",

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Culemann, S, Knab, K, Euler, M, Wegner, A, Garibagaoglu, H, Ackermann, J, Fischer, K, Kienhöfer, D, Crainiciuc, G, Hahn, J, Grüneboom, A, Nimmerjahn, F, Uderhardt, S, Hidalgo, A, Schett, G, Hoffmann, MH & Krönke, G 2023, 'Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes', Journal of Experimental Medicine, vol. 220, no. 6, e20220525. https://doi.org/10.1084/jem.20220525

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AU - Culemann, Stephan

AU - Knab, Katharina

AU - Euler, Maximilien

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AU - Garibagaoglu, Hilal

AU - Ackermann, Jochen

AU - Fischer, Kim

AU - Kienhöfer, Deborah

AU - Crainiciuc, Georgiana

AU - Hahn, Jonas

AU - Grüneboom, Anika

AU - Nimmerjahn, Falk

AU - Uderhardt, Stefan

AU - Hidalgo, Andrés

AU - Schett, Georg

AU - Hoffmann, Markus H.

AU - Krönke, Gerhard

PY - 2023/6/5

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AB - Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.

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Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this

Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

Projects

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this