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Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury.
Crit Care. 2015 Apr 03; 19:138.CC

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.

Authors

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Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25871971

Citation

Villar, Jesús, et al. "Tryptase Is Involved in the Development of Early Ventilator-induced Pulmonary Fibrosis in Sepsis-induced Lung Injury." Critical Care (London, England), vol. 19, 2015, p. 138.
Villar J, Cabrera-Benítez NE, Valladares F, et al. Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury. Crit Care. 2015;19:138.
Villar, J., Cabrera-Benítez, N. E., Valladares, F., García-Hernández, S., Ramos-Nuez, Á., Martín-Barrasa, J. L., Muros, M., Kacmarek, R. M., & Slutsky, A. S. (2015). Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury. Critical Care (London, England), 19, 138. https://doi.org/10.1186/s13054-015-0878-9
Villar J, et al. Tryptase Is Involved in the Development of Early Ventilator-induced Pulmonary Fibrosis in Sepsis-induced Lung Injury. Crit Care. 2015 Apr 3;19:138. PubMed PMID: 25871971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury. AU - Villar,Jesús, AU - Cabrera-Benítez,Nuria E, AU - Valladares,Francisco, AU - García-Hernández,Sonia, AU - Ramos-Nuez,Ángela, AU - Martín-Barrasa,José Luís, AU - Muros,Mercedes, AU - Kacmarek,Robert M, AU - Slutsky,Arthur S, Y1 - 2015/04/03/ PY - 2014/12/02/received PY - 2015/03/12/accepted PY - 2015/4/15/entrez PY - 2015/4/15/pubmed PY - 2016/1/5/medline SP - 138 EP - 138 JF - Critical care (London, England) JO - Crit Care VL - 19 N2 - 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. SN - 1466-609X UR - https://www.unboundmedicine.com/medline/citation/25871971/Tryptase_is_involved_in_the_development_of_early_ventilator_induced_pulmonary_fibrosis_in_sepsis_induced_lung_injury_ L2 - https://ccforum.biomedcentral.com/articles/10.1186/s13054-015-0878-9 DB - PRIME DP - Unbound Medicine ER -