Lung microenvironment profiles in mouse models of ARDS
CCCF ePoster library. Luo A. Oct 27, 2015; 117359; P71 Disclosure(s): This study was funded by the Canadian Institute of Heath Research
Alice Aili Luo
Alice Aili Luo
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Topic: Basic/Translational Science

Lung microenvironment profiles in mouse models of ARDS

Alice Aili Luo, D. Islam, A. Grassi, D. Toumpanakis, B. Han, J. Laffey, M. Liu, A. Slutsky, H. Zhang

Anaesthesiology and Critical Care Medicine, St. Michael's Hospital, Keenan Research Centre, Toronto, Canada | Institute of Medical Science, University of Toronto, Toronto, Canada | Critical Care Medicine, University of Milano, Milan, Italy | Critical Care and Pulmonary Services, University of Athens, Athens, Greece | Anaesthesiology, Keenan Research Centre, St. Michael's Hospital, Toronto, Canada | Anaesthesiology, St. Michael's Hospital, Toronto, Canada | Thoracic Surgery Research, Toronto General Hospital, Toronto, Canada | Critical Care Medicine, University of Toronto, Toronto, Canada | Anaesthesiology, St. Michael's Hospital, Toronto, Canada

Introduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder of the lungs presented by severe hypoxia, pulmonary edema and fibrosis(1). Other than protective ventilator strategies for supportive care, there is no proven pharmacological treatment for ARDS, and the mortality rate remains unacceptably high(2). Numerous initial insults including pulmonary and non-pulmonary origins may result in different lung microenvironment that cannot be treated with a strategy of one-size-fits-all that is current practice. We sought to characterize individual microenvironment for personalized medicine in the management of ARDS. The purpose of the present study is to improve our understanding of the signature microenvironment characteristics of different lung injuries in order to design a combination of pharmaceutical agents as a novel therapeutic approach specific to the different ARDS scenarios.


To determine the microenvironment profile in ARDS mice models.

Methods: Male C57BL/6J, age 14-16 weeks, were given 3.0mL/kg HCl (pH 1.0, 1.0N), 10mg/kg LPS, or mechanically ventilated for 2 hr on low (10cmH2O PIP, 3cmH2O PEEP, 120 RR) or high (22cmH2O PIP, 0cmH2O PEEP, 70 RR) pressure to mimic acid-, bacteria-, or ventilator- induced lung injury, respectively. Naïve mice or animals receiving saline served as control. Animals were monitored for 48 hr and sacrificed. Mice BAL fluid, blood, lungs, kidney, small intestine, and brain were collected for proteomic and immunological assessment by mass spectrometry, H&E staining and commercially available ELISAs, respectively.

Results: Mice mechanically ventilated with high pressure, or challenged with HCl or LPS exhibited a significant increase in protein, albumin, total cell count, and percentage neutrophil in the BAL fluid compared to naïve or saline control mice (Fig. 1A-E). Low pressure mechanical ventilation only induced a significant increase in total cell count and percentage neutrophil count (Fig. 1D-E). Microenvironment composition analysis in the 3 models showed HCl-model exhibited greater increases in protein numbers (12%) compared to LPS (8%) and MV (2%) models. Interestingly, a higher number of proteins were disappeared after MV (14%) compared to the instillation models (4%- HCl and 3%-LPS) (Fig. 2A). Further analysis showed that 54% of the increased proteins and 67% of the disappeared proteins were model-dependent and that the proteins were not shared between the models. In HCl model, the microenvironment demonstrated a significant decrease in glutathione-S-transferase omega 1 and SPA, and increase in fibrinogen and inter-a-trypsin inhibitor H4 (Fig. 2C).

Conclusion: Microenvironment profile differs in different models of ARDS. By correcting the microenvironment, it may provide a novel therapeutic intervention for ARDS through personalized medicine.


1. Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri VM. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012; 38: 1573-1582.

2. Ranieri VM, Slutsky AS. Protective ventilatory strategy for ARDS: physiological evaluation of the clinical trials. Monaldi Arch Chest Dis 1998; 53: 644-646.

3. Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 2008; 295: L379-399.

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