Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia - 10/07/16

Doi : 10.1016/j.jinf.2016.05.013

Roberto Cangemi ^a,^{^{d
Equally contributors.}}, Pasquale Pignatelli ^a,^{^{d
Equally contributors.}}, Roberto Carnevale ^a, Simona Bartimoccia ^a, Cristina Nocella ^a, Marco Falcone ^b, Gloria Taliani ^c, Francesco Violi ^a,^⁎
and
the SIXTUS Study Group^{^e}
SIXTUS (thromboSIs-related eXTra-pulmonary oUtcomeS in pneumonia) study group: Simona Battaglia, Giuliano Bertazzoni, Elisa Biliotti, Cinzia Myriam Calabrese, Marco Casciaro, Maurizio De Angelis, Paolo De Marzio, Rozenn Esvan, Lucia Fazi, Domenico Ferro, Lucia Fontanelli Sulekova, Cristiana Franchi, Laura Giordo, Stefania Grieco, Elisa Manzini, Sergio Morelli, Paolo Palange, Daniele Pastori, Marco Rivano Capparuccia, Giulio Francesco Romiti, Elisabetta Rossi, Eleonora Ruscio, Alessandro Russo, Maria Gabriella Scarpellini, Stefano Trapè, Filippo Toriello.
Simona Battaglia ^f, Giuliano Bertazzoni ^f, Elisa Biliotti ^f, Cinzia Myriam Calabrese ^f, Marco Casciaro ^f, Maurizio De Angelis ^h, Paolo De Marzio ^f, Rozenn Esvan ^h, Lucia Fazi ^f, Domenico Ferro ^f, Lucia Fontanelli Sulekova ^h, Cristiana Franchi ^h, Laura Giordo ^f, Stefania Grieco ^h, Elisa Manzini ^f, Sergio Morelli ^f, Paolo Palange ^g, Daniele Pastori ^f, Marco Rivano Capparuccia ^h, Giulio Francesco Romiti ^f, Elisabetta Rossi ^f, Eleonora Ruscio ^f, Alessandro Russo ^g, Maria Gabriella Scarpellini ^f, Stefano Trapè ^f, Filippo Toriello ^f
^f Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
^g Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy
^h Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Italy

^a Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
^b Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy
^c Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Italy

^∗Corresponding author. I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Roma 00161, Italy. Tel.: +39 064461933; fax: +39 0649970103.I Clinica MedicaSapienza University of RomeViale del Policlinico 155Roma00161Italy

Summary

Objectives

Platelet activation seems to be implicated in the cardiovascular events occurring in patients with community-acquired pneumonia (CAP) but the underlying mechanism is still unclear. Aim of the study was to assess the mechanism involved in platelet activation in CAP patients.

Methods

Two-hundred-seventy-eight consecutive patients hospitalized for CAP were recruited and followed-up until discharge. Hospitalized patients matched for sex, age and comorbidities but without acute infectious diseases were used as controls.

Results

At hospital admission patients disclosed enhanced plasma levels of sP-selectin, a maker of in-vivo platelet activation, serum sNOX2-dp, a marker of NADPH-oxidase activation, serum Lipopolysaccharide (LPS) and serum zonulin, a marker of gut permeability, compared to controls (p < 0.001). Baseline sP-selectin was independently associated to serum LPS, sNOX2-sp and Pneumonia Severity Index score (p < 0.001). Plasma sP-selectin, serum sNOX2-dp, LPS and zonulin coincidentally decreased at hospital discharge (p < 0.001). An in vitro study showed that LPS, at concentration similar to that found in CAP patients, induced sP-selectin release by agonist-activated platelets, a phenomenon that was counteract by treating cells with gp91ds-tat, a specific inhibitor of NOX2.

Conclusions

CAP patients display enhanced platelet activation, which is related to LPS-mediated NOX2 activation. Enhanced gut permeability seems be implicated in enhancing circulating levels of LPS.

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Highlights

•	Platelet activation seems to be implicated in the CAP related cardiovascular risk.
•	We found that bacterial LPS was elevated in the early phase of CAP.
•	LPS significantly correlated with platelet activation and NOX2 activity.
•	In vitro study showed that LPS induced sP-selectin release, via NOx2 upregulation.
•	A marker of gut permeability was increased and paralleled those of LPS.

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Keywords : Pneumonia, Blood platelets, P-selectin, Endotoxins, NADPH oxidase

Plan

Introduction

Material and methods

Patients

Soluble P-selectin and NOX2 and LPS and zonulin blood levels

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Vol 73 - N° 2

P. 107-114 - août 2016 Retour au numéro

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Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia - 10/07/16

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Plan

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