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Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor

Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced p...

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Autores principales: Waller, Amie K., Sage, Tanya, Kumar, Christopher, Carr, Thomas, Gibbins, Jonathan M., Clarke, Simon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836464/
https://www.ncbi.nlm.nih.gov/pubmed/23911710
http://dx.doi.org/10.1093/infdis/jit398
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author Waller, Amie K.
Sage, Tanya
Kumar, Christopher
Carr, Thomas
Gibbins, Jonathan M.
Clarke, Simon R.
author_facet Waller, Amie K.
Sage, Tanya
Kumar, Christopher
Carr, Thomas
Gibbins, Jonathan M.
Clarke, Simon R.
author_sort Waller, Amie K.
collection PubMed
description Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a Western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced hemostasis in a mouse tail-bleed assay.
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spelling pubmed-38364642013-11-22 Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor Waller, Amie K. Sage, Tanya Kumar, Christopher Carr, Thomas Gibbins, Jonathan M. Clarke, Simon R. J Infect Dis Major Articles and Brief Reports Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a Western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced hemostasis in a mouse tail-bleed assay. Oxford University Press 2013-12-15 2013-08-02 /pmc/articles/PMC3836464/ /pubmed/23911710 http://dx.doi.org/10.1093/infdis/jit398 Text en © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Waller, Amie K.
Sage, Tanya
Kumar, Christopher
Carr, Thomas
Gibbins, Jonathan M.
Clarke, Simon R.
Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title_full Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title_fullStr Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title_full_unstemmed Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title_short Staphylococcus aureus Lipoteichoic Acid Inhibits Platelet Activation and Thrombus Formation via the Paf Receptor
title_sort staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the paf receptor
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836464/
https://www.ncbi.nlm.nih.gov/pubmed/23911710
http://dx.doi.org/10.1093/infdis/jit398
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