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

Author:

Culemann Stephan12ORCID,Knab Katharina12ORCID,Euler Maximilien12ORCID,Wegner Anja12ORCID,Garibagaoglu Hilal12ORCID,Ackermann Jochen12ORCID,Fischer Kim12ORCID,Kienhöfer Deborah12ORCID,Crainiciuc Georgiana3ORCID,Hahn Jonas12ORCID,Grüneboom Anika12ORCID,Nimmerjahn Falk4ORCID,Uderhardt Stefan12ORCID,Hidalgo Andrés35ORCID,Schett Georg12ORCID,Hoffmann Markus H.126ORCID,Krönke Gerhard12ORCID

Affiliation:

1. Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen 1 , Erlangen, Germany

2. Deutsches Zentrum für Immuntherapie, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen 2 , Erlangen, Germany

3. Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III 3 , Madrid, Spain

4. Institute of Genetics at the Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg 4 , Erlangen, Germany

5. Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine 5 , New Haven, CT, USA

6. Department of Dermatology, Allergy and Venerology, University of Lübeck 6 , Lübeck, Germany

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.

Funder

Deutsche Forschungsgemeinschaft

Friedrich-Alexander University Erlangen-Nürnberg

Bundesministerium für Bildung und Forschung

European Union

National Institutes of Health

National Institute of Allergy and Infectious Diseases

European Commission

Ministerio de Ciencia e Innovacion

Fundacion La Caixa

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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