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Mediators Released from LPS‐challenged Lungs into Circulation Induce the Inflammatory Response in Liver Vascular Endothelial Cells
Author(s) -
Markovic Nevena,
McCaig Lynda A,
Veldhuizen Ruud AW,
Lewis James F,
Cepinskas Gediminas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.741.7
Subject(s) - ards , lung , inflammation , medicine , immunology , lipopolysaccharide , pathology
Acute respiratory distress syndrome (ARDS) contributes significantly to the development of systemic inflammation and subsequent multiple organ dysfunction syndrome (MODS). However, the role of lung‐derived inflammatory mediators on modulation of the inflammatory response in remote organs is poorly understood. In this study, lung inflammation in mice was induced by intranasal LPS (1mg/kg) administration. Four hours later, the isolated‐perfused mouse lung approach was employed to collect mediator(s) secreted by the inflamed lung into systemic circulation (pulmonary circulation perfusate). Perfusate was used to investigate the effects of lung mediators on induction of the inflammatory response in the liver. To this end, primary mouse liver vascular endothelial cells (LVEC) in vitro were stimulated with perfusate and assessed for expression of the pro‐inflammatory phenotype. Exposure of LVEC to perfusate from LPS‐challenged lungs for 4 h resulted in: 1) increased ROS production (Lucigenin assay), 2) activation of NF¿B (Immunocytochemistry), 3) up‐regulation of pro‐adhesive phenotype (E‐selectin, ICAM‐1 and VCAM‐1 expression; RT‐PCR, cell ELISA) and 4) increased 51 Cr‐neutrophil adhesion to LVEC. These data provide with insight into the molecular mechanisms associated to lung‐induced remote organ (liver) injury during ARDS/MODS (HSFO NA6171, MOP 11666).