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), thromboxane (Tx)A2 (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.

Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production / Nocella, Cristina; Carnevale, Roberto; Bartimoccia, Simona; Novo, Marta; Cangemi, Roberto; Pastori, Daniele; Calvieri, Camilla; Pignatelli, Pasquale; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 117:7(2017). [10.1160/TH16-11-0857]

Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production

NOCELLA, CRISTINA;CARNEVALE, Roberto
Co-primo
;
BARTIMOCCIA, SIMONA;NOVO, MARTA;CANGEMI, ROBERTO;PASTORI, DANIELE;CALVIERI, CAMILLA;PIGNATELLI, Pasquale;VIOLI, Francesco
2017

Abstract

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), thromboxane (Tx)A2 (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.
2017
LPS; community-acquired pneumonia; oxidative stress; platelet activation
01 Pubblicazione su rivista::01a Articolo in rivista
Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production / Nocella, Cristina; Carnevale, Roberto; Bartimoccia, Simona; Novo, Marta; Cangemi, Roberto; Pastori, Daniele; Calvieri, Camilla; Pignatelli, Pasquale; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 117:7(2017). [10.1160/TH16-11-0857]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/966372
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