Conditioned media from adipose stromal cells limit lipopolysaccharide-induced lung injury, endothelial hyperpermeability and apoptosis.

Abstract

BACKGROUND:

Acute Respiratory Distress Syndrome (ARDS) is a condition that contributes to morbidity and mortality of critically ill patients. We investigated whether factors secreted by adipose stromal cells (ASC) into conditioned media (ASC-CM) will effectively decrease lung injury in the model of lipopolysaccharide (LPS)-induced ARDS.

METHODS:

To assess the effect of ASC-CM on ARDS indices, intravenous delivery of ASC and ASC-CM to C57Bl/6 mice was carried out 4 h after LPS oropharyngeal aspiration; Evans Blue Dye (EBD) was injected intravenously 1 h prior to animal sacrifice (48 h post-LPS). Lungs were either fixed for histopathology, or used to extract bronchoalveolar lavage fluid (BALF) or EBD. To assess the effect of ASC-CM on endothelial barrier function and apoptosis, human pulmonary artery endothelial cells were treated with ASC-CM for 48-72 h.

RESULTS:

ASC-CM markedly reduced LPS-induced histopathologic changes of lung, protein extravasation into BALF, and suppressed the secretion of proinflammatory cytokines TNFα and IL6. White Blood Cells (WBC) from BALF of LPS-challenged mice receiving ASC-CM had decreased reactive oxygen species (ROS) generation compared to WBC from LPS-challenged mice receiving control media injection. Treatment of pulmonary endothelial monolayers with ASC-CM significantly suppressed H2O2-induced leakage of FITC dextran and changes in transendothelial resistance, as well as gap formation in endothelial monolayer. ASC-CM exposure reduced the percentage of endothelial cells expressing ICAM-1, and suppressed TNFα-induced expression of E-selectin and cleavage of caspase-3. ASC-CM reduced the endothelial level of pro-apoptotic protein Bim, but did not affect the level of Bcl-2, Bad, or Bad phosphorylation.

CONCLUSIONS:

Factors secreted by ASC efficiently reduce ARDS indices, endothelial barrier hyperpermeability, and activation of pro-inflammatory and pro-apoptotic pathways in endothelium.

• Authors: Hongyan Lu, Christophe Poirier, Todd Cook, Dmitry O Traktuev, Stephanie Merfeld-Clauss, Benjamin Lease, Irina Petrache, Keith L March, Natalia V Bogatcheva
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 67 (Feb 21 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 25889857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Culture Media, Conditioned
• Cytokines
• E-Selectin
• Inflammation Mediators
• Lipopolysaccharides
• SELE protein, human
• Intercellular Adhesion Molecule-1

Topics

• Acute Lung Injury (pathology)
• Adipose Tissue (cytology)
• Animals
• Apoptosis (drug effects)
• Biomarkers (metabolism)
• Bronchoalveolar Lavage Fluid
• Cell Membrane Permeability (drug effects)
• Culture Media, Conditioned (pharmacology)
• Cytokines (metabolism)
• E-Selectin (metabolism)
• Endothelial Cells (drug effects, pathology)
• Flow Cytometry
• Humans
• Inflammation Mediators (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Leukocyte Count
• Lipopolysaccharides
• Lung (drug effects, pathology)
• Male
• Mice, Inbred C57BL
• Neutrophil Infiltration (drug effects)
• Pulmonary Artery (pathology)
• Stromal Cells (metabolism)