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Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury

Authors: Jesús Villar, Nuria E Cabrera-Benítez, Francisco Valladares, Sonia García-Hernández, Ángela Ramos-Nuez, José Luís Martín-Barrasa, Mercedes Muros, Robert M Kacmarek, Arthur S Slutsky

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Most patients with sepsis and acute lung injury require mechanical ventilation to improve oxygenation and facilitate organ repair. Mast cells are important in response to infection and resolution of tissue injury. Since tryptase secreted from mast cells has been associated with tissue fibrosis, we hypothesized that tryptase would be involved in the early development of ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis-induced lung injury.

Methods

Prospective, randomized, controlled animal study using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. Animals were randomized to spontaneous breathing or two ventilatory strategies for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH2O positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20 ml/kg plus 2 cmH2O PEEP. Healthy, non-ventilated animals served as non-septic controls. We studied the following end points: histology, serum cytokine levels, hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2) protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical localization in the lungs.

Results

All septic animals developed acute lung injury. Animals ventilated with high VT had a significant increase of pulmonary fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to septic controls (P <0.0001). However, protective ventilation attenuated sepsis-induced lung injury and decreased lung tryptase and PAR-2 protein levels. Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the lungs.

Conclusions

Mechanical ventilation modified tryptase and PAR-2 in injured lungs. Increased levels of these proteins were associated with development of sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis-induced lung injury.
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Metadata
Title
Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury
Authors
Jesús Villar
Nuria E Cabrera-Benítez
Francisco Valladares
Sonia García-Hernández
Ángela Ramos-Nuez
José Luís Martín-Barrasa
Mercedes Muros
Robert M Kacmarek
Arthur S Slutsky
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0878-9

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