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Critical Care
Published in: Critical Care 4/2011

Open Access 01-08-2011 | Research

The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis

Authors: Margarita Pérez-Casal, Victoria Thompson, Colin Downey, Ingeborg Welters, Duncan Wyncoll, Jecko Thachil, Cheng Hock Toh

Published in: Critical Care | Issue 4/2011

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Abstract

Introduction

Activated protein C (APC) induces release of microparticles (MP) from primary physiological cells, which are found in patients undergoing treatment with recombinant human APC (rhAPC) for severe sepsis. We hypothesised that APC on these circulating MPs activate endothelial protease-activated receptor 1 (PAR1) to induce anti-apoptotic and anti-inflammatory properties that can improve patient outcome.

Methods

This was an experimental study on clinical samples in an intensive care setting, and included patients with severe sepsis who fulfilled criteria for treatment with rhAPC. The number of CD13+ MPs from the patients were analysed to determine their origin. They were also quantified for endothelial protein C receptor (EPCR) and APC expression. Clinical relevance of these MPs were ascertained by comparing survival between the group receiving rhAPC (n = 25) and a control group of untreated patients (n = 25). MPs were also incubated with endothelial cells to analyse apoptotic gene expression, cytoprotection and anti-inflammatory effects.

Results

rhAPC treatment induced a significant increase in circulating MP-associated EPCR by flow cytometry (P < 0.05) and by quantitative ELISA (P < 0.005). APC expression also showed significant increases (P < 0.05). Numerically, CD13+ MPs were higher in rhAPC-treated survivors versus non-survivors. However, the number of non-survivors was low and this was not significantly different. APC on MPs was demonstrated to induce anti-apoptotic and endothelial barrier effects through the activation of endothelial PAR1.

Conclusions

rhAPC treatment in patients with sepsis significantly increases circulating EPCR + MPs. These MPs were noted to express APC, which has specific anti-apoptotic and anti-inflammatory effects, with a non-significant correlative trend towards survival. This suggests that MPs could disseminate APC function and activate endothelial PAR1 at distal vascular sites.
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Metadata
Title
The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis
Authors
Margarita Pérez-Casal
Victoria Thompson
Colin Downey
Ingeborg Welters
Duncan Wyncoll
Jecko Thachil
Cheng Hock Toh
Publication date
01-08-2011
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2011
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc10356

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