Abstract

This project of the UCSD/ACUTE Lung Injury SCOR focuses on the prevention or amelioration of acute lung injury using targeted interventions based on observations which define the specific mechanisms responsible for acute lung injury. The human model used for these projects consists of patients undergoing pulmonary thromboendarterectomy (PT-E). Up to 60 percent of these patients develop a high permeability edema/reperfusion lung injury following PT-E.
The aims of this project are to continue to define this unique, predictable, model of lung injury in PT-E patients by collecting sequential blood and BALF samples from PT-E and other patients at risk for ARDS and analyzing these samples for markers of ALI [neutrophil and protein influx, cytokines (IL-8, TNF-alpha), oxidized alpha1-proteinase inhibitor, glutathione levels, and soluble adhesion molecules (E-P-, L-selectins, ICAM-1, VCAM-1)]. The three interventional trials proposed analog, (2) use of an anti-oxidant drug, and (3) inhaled nitric oxide in the prevention of reperfusion of reperfusion lung injury. In addition to assessing the efficacy and safety of these three interventions, serial blood and bronchoalveolar lavage specimens will be collected prior to, during the acute phase, and during resolution of acute lung injury. Analysis of these specimens will provide insights into the cellular components and mediators that are involved in the initiation and perpetuation of acute lung injury. These specimens will be shared with collaborators working on other SCOR projects at UCSD and, if desired, with other Acute Lung Injury SCORs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL023584-23
Application #
6418789
Study Section
Project Start
2000-12-01
Project End
2001-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
23
Fiscal Year
2001
Total Cost
$40,863
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Kerr, Kim M; Auger, William R; Marsh, James J et al. (2012) Efficacy of methylprednisolone in preventing lung injury following pulmonary thromboendarterectomy. Chest 141:27-35
Spragg, Roger G; Ponganis, Paul J; Marsh, James J et al. (2004) Surfactant from diving aquatic mammals. J Appl Physiol 96:1626-32
Dunzendorfer, Stefan; Lee, Hyun-Ku; Soldau, Katrin et al. (2004) TLR4 is the signaling but not the lipopolysaccharide uptake receptor. J Immunol 173:1166-70
Dunzendorfer, Stefan; Lee, Hyun-Ku; Soldau, Katrin et al. (2004) Toll-like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS responses. FASEB J 18:1117-9
Lee, Hyun-Ku; Dunzendorfer, Stefan; Tobias, Peter S (2004) Cytoplasmic domain-mediated dimerizations of toll-like receptor 4 observed by beta-lactamase enzyme fragment complementation. J Biol Chem 279:10564-74
Spragg, Roger G; Lewis, James F; Wurst, Wilhelm et al. (2003) Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med 167:1562-6
Thompson, Patricia A; Tobias, Peter S; Viriyakosol, Suganya et al. (2003) Lipopolysaccharide (LPS)-binding protein inhibits responses to cell-bound LPS. J Biol Chem 278:28367-71
Tapping, Richard I; Tobias, Peter S (2003) Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling. J Endotoxin Res 9:264-8
Bussolati, Benedetta; David, Salvatore; Cambi, Vincenzo et al. (2002) Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. Int J Mol Med 10:441-9
Li, Jiali; Marsh, James J; Spragg, Roger G (2002) Effect of CTP:phosphocholine cytidylyltransferase overexpression on the mouse lung surfactant system. Am J Respir Cell Mol Biol 26:709-15

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