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Original research
Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity
  1. Inga Wessels1,
  2. Johanna Theresa Pupke2,
  3. Klaus-Thilo von Trotha2,3,
  4. Alexander Gombert2,
  5. Anika Himmelsbach4,
  6. Henrike Josephine Fischer1,
  7. Michael J Jacobs2,
  8. Lothar Rink1,
  9. Jochen Grommes2,5
  1. 1 Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Nordrhein-Westfalen, Germany
  2. 2 Department of Vascular Surgery, Medical Faculty, RWTH Aachen University, Aachen, Nordrhein-Westfalen, Germany
  3. 3 Department of Vascular Surgery, Marienhospital Aachen, Aachen, Nordrhein-Westfalen, Germany
  4. 4 Department of Cardiology, Medical Clinic I, Medical Faculty, RWTH Aachen University, Aachen, Nordrhein-Westfalen, Germany
  5. 5 Department of Vascular Surgery, Rhein-Maas Klinikum GmbH, Wurselen, Nordrhein-Westfalen, Germany
  1. Correspondence to Professor Jochen Grommes, Department of Vascular Surgery, Rhein-Maas Klinikum GmbH, Wurselen, Nordrhein-Westfalen, Germany; Jochen.Grommes{at}rheinmaasklinikum.de

Abstract

Introduction Zinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested.

Methods 64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well.

Results Injecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail.

Conclusion Zinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.

  • cytokine biology
  • innate immunity
  • neutrophil biology
  • respiratory infection
  • bacterial infection
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Footnotes

  • Contributors Gabriela Engelhardt and Zohreh Packsereshtmogharab contributed excellent technical assistance. Oliver Pabst, flow cytometry facility of the UK Aachen supported FACS measurements. Dr Singh, DWI – Leibniz Institute for Interactive Materials, RWTH Aachen University, kindly providing NCI-H441 cells.

  • Funding This study was funded by START-Program of the Faculty of Medicine, RWTH Aachen (grant number:116/16).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethics approval obtained from the local ethical authorities for all experiments (Landesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen AZ 84–02.04.2013–3062) and ethics committee (RWTH Aachen University Hospital, statement no. EK 023/05).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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