Panton-Valentine Leukocidin associated with S. aureus osteomyelitis activates platelets via neutrophil secretion products

Silke Niemann, Anne Bertling, Martin F Brodde, Anke C Fender, Hélène Van de Vyver, Muzaffar Hussain, Dirk Holzinger, Dirk Reinhardt, Georg Peters, Christine Heilmann, Bettina Löffler, Beate E Kehrel

27 Citationer (Scopus)

Abstrakt

Globalization and migration promote the spread of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. The toxin PVL is linked to the development of thrombosis in association with osteomyelitis. The mechanisms by which PVL drives thrombosis development are however still unknown. We demonstrate that PVL-damaged neutrophils activate platelets via neutrophil secretion products, such as α-defensins and the myeloperoxidase product HOCl, as well as the formation of HOCl-modified proteins. Neutrophil damage by PVL is blocked by anti-PVL-antibodies, explaining why especially young osteomyelitis patients with a low antibody titre against PVL suffer from thrombotic complications. Platelet activation in the presence of PVL-damaged neutrophils is prevented by α-defensin inhibitors and by glutathione and resveratrol, which are both inhibitors of HOCl-modified protein-induced platelet activation. Remarkably, intravenously infused glutathione also prevents activation of human platelets in an ex vivo assay. We here describe a new mechanism of PVL-neutrophil-platelet interactions, which might be extrapolated to other toxins that act on neutrophils. Our observations may make us think about new approaches to treat and/or prevent thrombotic complications in the course of infections with PVL-producing S. aureus strains.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind8
Udgave nummer1
Sider (fra-til)2185
ISSN2045-2322
DOI
StatusUdgivet - 1 feb. 2018
Udgivet eksterntJa

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