It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Institute of Medical Microbiology, University of Muenster, Muenster, Germany
2 Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University of Muenster, Muenster, Germany; Interdisciplinary Center for Clinical Research (IZKF) Muenster, Muenster, Germany
3 Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University of Muenster, Muenster, Germany
4 Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany
5 Institute of Medical Microbiology, University of Muenster, Muenster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Muenster, Germany
6 Institute of Medical Microbiology, University of Muenster, Muenster, Germany; Interdisciplinary Center for Clinical Research (IZKF) Muenster, Muenster, Germany
7 Institute of Medical Microbiology, Jena University Hospital, Jena, Germany