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.
Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes
Disclosures: The authors declare no competing interests exist.
Stephan Culemann’s current affiliation is Immunology of Aging, Leibniz Institute on Aging – Fritz-Lipmann-Institute, Jena, Germany.
- Award Id(s): FG 2886 “PANDORA” – B01/B02/A03/B04,CRC1181-A03/A01/A02/A07/C03 Z2
- Award Id(s): EFI_Verbund_Med_05_MIRACLE
- Award Id(s): MASCARA,MelAutim
- Award Id(s): Horizon 2020 ERC-2014-StG 640087 – SOS,ERC-2020-CoG 101001866 – INSPIRE,ERC-2018-SyG nanoSCOPE,RTCure
- Award Id(s): R01AI165661
- Award Id(s): 861878
- Award Id(s): CEX2020-001041-S
- Award Id(s): HR17_00527
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; Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes. J Exp Med 5 June 2023; 220 (6): e20220525. doi: https://doi.org/10.1084/jem.20220525
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