title: 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.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. honlu@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. honlu@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. honlu@iu.edu.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Indiana University, Indianapolis, IN, USA. poirierc@iu.edu.
authors.forename: Christophe
authors.initials: C
authors.lastname: Poirier
authors.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. tgcook@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. tgcook@iu.edu.
authors.forename: Todd
authors.initials: T
authors.lastname: Cook
authors.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. tdmitry@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. tdmitry@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. tdmitry@iu.edu.
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Traktuev
authors.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. smerfeld@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. smerfeld@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. smerfeld@iu.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Merfeld-Clauss
authors.affiliation: Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. benlease@iupui.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lease
authors.affiliation: Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. ipetrach@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. ipetrach@iu.edu.|Division of Pulmonary and Critical Care Medicine, Indiana University, Indianapolis, IN, USA. ipetrach@iu.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrache
authors.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. kmarch@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. kmarch@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. kmarch@iu.edu.
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
authors.affiliation: Division of Cardiology, Indiana University, Indianapolis, IN, USA. nbogatch@iu.edu.|Indiana Center for Vascular Biology and Medicine and VC-CAST Signature Center, Indianapolis, IN, USA. nbogatch@iu.edu.|Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. nbogatch@iu.edu.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Bogatcheva
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002463:Cell Membrane Permeability / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D011651:Pulmonary Artery / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D016207:Cytokines; D019040:E-Selectin; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C546936:SELE protein, human; D018799:Intercellular Adhesion Molecule-1