Published ahead of print on March 2, 2006, doi:10.1164/rccm.200511-1737OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200511-1737OC
Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung InjuryDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, University of Chicago, Chicago, Illinois; Department of Vascular Biology and Thrombosis Research, University of Vienna, Vienna, Austria; and Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia Correspondence and requests for reprints should be addressed to Konstantin Birukov, M.D., Ph.D., Section of Pulmonary and Critical Medicine, Department of Medicine, Division of Biomedical Sciences, University of Chicago, 929 East 57th Street, CIS Bldg., W410, Chicago IL 60637. E-mail: kbirukov{at}medicine.bsd.uchicago.edu Rationale: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. Objective: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. Methods: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5–6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction.
Measurements and Main Results: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1 Conclusions: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.
Key Words: bacterial wall lipopolysaccharide • bronchoalveolar lavage • interleukin 6 • interleukin 1 This article has been cited by other articles:
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, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. 
