The long term objective of this proposal is to evaluate the potential contribution of the """"""""activated"""""""" alveolar macrophage (A-Mo) in producing the lung injury that commonly complicates recovery from severe trauma or burns. In this clinical setting, the patients are frequently septic with a concomitant endotoxemia and/or sustained for prolonged periods with high FI02 ventilation to correct hypoxemia. Both endotoxin (LPS) and oxygen metabolites are known to stimulate Mo and are also associated with acute lung injury. A-Mo will be stimulated with LPS and 02 intermediates both in vitro and in vivo and the ability of A-Mo to produce: 1) procoagulant activity, 2) cytotoxic agents, and 3) fibroblast growth factor(s) will be confirmed in vitro and the in vivo. Attempts will then be made to block these products in vitro, utilizing agents from one of three groups known to modulate Mo functions: 1) corticosteroids, 2) non-steroidal anti-inflammatory drugs (NSAID) and 3) scavengers of O2 intermediates. The inhibitors of mediator production in vitro will then be tested in vivo. Potential amelioration of lung injury will be correlated with microscopic (light and electron) and pulmonary hemodynamic and respiratory changes (utilizing a chronic lung lymph fistula) between inhibitor pretreated and untreated animals. The goal is thus to confirm the association of the production of deleterious mediators by A-Mo and acute lung injury, and correlate inhibition of these products with an amelioration of the acute lung injury by both anatomic and physiologic criteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035361-02
Application #
3287964
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-04-01
Project End
1991-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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