The long range goal of the proposed study is to facilitate successful lung transplantation by improving methods for lung preservation and improving early lung function following transplantation. Achievement of these goals would facilitate the logistics of organ retrieval and improve utilization of the current donor pool. Furthermore improved early graft function would reduce morbidity and mortality following lung transplantation. The research plan has two components: 1) To characterize alterations occurring in the lung during preservation with specific reference to vascular endothelium. This will involve analysis of functional changes (measurement of permeability) and alterations of vascular endothelial cell surface proteins (intercellular adhesion molecules) which play a role in leukocyte-mediated injury following reperfusion. 2) To explore the use of specific strategies to reduce or eliminate leukocyte-endothelial interactions following reperfusion. These interventions include the use of monoclonal antibodies against adhesion molecules; pharmacologic inhibition of neutrophil activation and cytokine release; and use of monoclonal antibodies directed against tumor necrosis factor, a cytokine which plays a major role in leukocyte-mediated injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL041281-05
Application #
2219955
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1990-09-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Suda, Takashi; Daddi, Niccolo'; Tagawa, Tsutomu et al. (2005) Recipient intramuscular cotransfection of transforming growth factor beta1 and interleukin 10 ameliorates acute lung graft rejection. J Thorac Cardiovasc Surg 129:926-31
Kuo, Elbert; Bharat, Ankit; Dharmarajan, Sekhar et al. (2005) Animal models for bronchiolitis obliterans syndrome following human lung transplantation. Immunol Res 33:69-81
Tagawa, Tsutomu; Kozower, Benjamin D; Kanaan, Samer A et al. (2004) Gene transfer of tumor necrosis factor inhibitor improves the function of lung allografts. J Thorac Cardiovasc Surg 127:1558-63
Tagawa, Tsutomu; Dharmarajan, Sekhar; Hayama, Makio et al. (2004) Endobronchial gene transfer of soluble type I interleukin-1 receptor ameliorates lung graft ischemia-reperfusion injury. Ann Thorac Surg 78:1932-9; discussion 1939

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