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Thromb Haemost 2017; 117(08): 1558-1570
DOI: 10.1160/TH16-11-0857
Cellular Haemostasis and Platelets
Schattauer GmbH

Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production

Cristina Nocella
1   Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
2   Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
,
Roberto Carnevale
2   Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
,
Simona Bartimoccia
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Marta Novo
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Roberto Cangemi
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Daniele Pastori
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Camilla Calvieri
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Pasquale Pignatelli
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
,
Francesco Violi
3   Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
› Author Affiliations
Further Information

Publication History

Received: 15 November 2016

Accepted after major revision: 09 April 2017

Publication Date:
22 November 2017 (online)

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Summary

The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; p<0.01). Ex vivo study showed that agonist-stimulated platelets were associated with enhanced PA (p<0.01), Toll-like receptor 4 (TLR4) expression (p<0.05), TxA2 (p<0.01) and 8-iso-PGF2α-III (p<0.01) production in CAP patients compared to controls. The study provides evidence that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggests LPS as a potential trigger for PA in CAP.

Supplementary Material to this article is available online at www.thrombosis-online.com

Keywords

LPS - platelet activation - oxidative stress - community-acquired pneumonia

 

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