Lipid nanotubes unmask neutrophils for complement attack

Blood, vol. 147, pp. 1338–1350

Abstract

ABSTRACT: Neutrophils, critical components of innate immunity, undergo significant morphological changes during phagocytosis. In this study, we demonstrate that neutrophils exposed to shear stress generate lipid nanotubes (NTs) with a unique composition. Compared with the proteome of whole neutrophils, NTs notably lack cytoskeletal elements and the complement-inhibiting transmembrane protein CD46. Consequently, these NTs are recognized by the complement system and selectively opsonized the complement component C3b. Biophysical characterization of NTs confirmed that their integrity relies on lipid-lipid interactions and that they pinch off from neutrophils to form NT-derived vesicles (NTDVs). We detected C3b+ NTDVs in plasma from patients and animal models experiencing diverse inflammatory conditions, including metastatic melanoma, vasculitis, and polytrauma. Further functional experiments indicate that resting neutrophils phagocytose complement-opsonized NTDVs, leading to cell activation, including the production of reactive oxygen species. In conclusion, our data suggest a significant role for neutrophil-derived NTs in a wide range of inflammatory diseases and reveal a previously unknown mode of cell-cell communication.

Authors 15

1. Xiaobo Liu

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   1Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   University Hospital Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany

2. Yuanyuan Wang

   Universität Hamburg · University Medical Center Hamburg-Eppendorf · University Cancer Center Hamburg

   Affiliation as printed

   1Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   2Mildred Scheel Cancer Career Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   University Hospital Hamburg-Eppendorf, Hamburg, Germany

3. Alexander Thomas Bauer

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   1Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   University Hospital Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany

4. Alex Márki

   MedStar Georgetown University Hospital

   Affiliation as printed

   3Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, Washington, DC

   MedStar Georgetown University Hospital, Washington, Washington, United States

5. Christian F. Krebs

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   4Department of Medicine III, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   5Hamburg Center for Translational Immunology, Hamburg, Germany

   University Medical Center Hamburg-Eppendorf, Hamburg, Germany

6. Karsten Häffner

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   6Department of Internal Medicine IV (Nephrology), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

   University of Freiburg, Faculty of Medicine, Freiburg, Germany

7. Bente Siebels

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   7Section of Mass Spectrometry and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   University Medical Center Hamburg-Eppendorf, Hamburg, Germany

8. Hartmut Schlüter

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   7Section of Mass Spectrometry and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

   University Medical Center Hamburg (UKE), Hamburg, Germany

9. Frank Hildebrand Aachen 8Department of Orthopedics Trauma and Reconstructive Surgery

   RWTH Aachen University

   Affiliation as printed

   8Department of Orthopedics, Trauma and Reconstructive Surgery, Rheinisch-Westfalische Technische Hochschule Aachen University, Aachen, Germany

   RWTH Aachen University, Aachen, Germany

10. Rebecca Halbgebauer

    Universität Ulm · University Hospital Ulm

    Affiliation as printed

    9Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany

    Ulm University Hospital, Ulm, Germany

11. Markus Stefan Huber-Lang

    Universität Ulm · University Hospital Ulm

    Affiliation as printed

    9Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany

    University Hospital Ulm, Germany, Ulm, Germany

12. Klaus F. Ley

    Augusta University

    Affiliation as printed

    10Immunology Center of Georgia, Augusta University, Augusta, GA

    Augusta University, Augusta, Georgia, United States

13. Matthias F. Schneider

    TU Dortmund University

    Affiliation as printed

    11Medical and Biological Physics, Department of Physics, Technische Universität Dortmund University, Dortmund, Germany

    Tu Dortmund, Dortmund, Germany

14. Stefan W. Schneider

    University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    1Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    University Hospital Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany

15. Christian Gorzelanny

    University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    1Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    University Hospital Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany