Significant lung dysfunction results from Pneumocystis carinii pneumonia in immunocompromised patients. Despite the magnitude of this problem, little is known of the mechanisms by which Pneumocystis carinii produces this lung dysfunction. The proposed study will test the hypothesis that Pneumocystis carinii interacts with alveolar Type II cells which synthesize and secrete surfactant-associated phospholipids and proteins to produce the lung dysfunction observed in Pneumocystis carinii pneumonia. Systematic studies will be undertaken to identify developmental stages and specific components of Pneumocystis carinii responsible for inhibition of Type II cell function. A biochemical characterization of the inhibitory components will be undertaken and the mechanism by which Pneumocystis carinii influences Type II cell production of phospholipids and surfactant-associated proteins will be determined. Polyclonal and monoclonal antibodies directed against components of Pneumocystis carinii will be utilized to define specific epitopes involved in regulation of Type II cell function. These in vitro studies will then be correlated with an in vivo model of Pneumocystis carinii pneumonia in the rat, to determine whether in vitro observations with isolated Type II cells are relevant to the intact animal. The overall objective of these studies is to determine cellular mechanisms involved in production of lung dysfunction during Pneumocystis carinii pneumonia. The data obtained will be invaluable in designing rational therapeutic approaches for immunocompromised patients with Pneumocystis carinii pneumonia and will further our understanding of factors regulating surfactant production by the alveolar Type II cell.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL046653-04
Application #
2223104
Study Section
Special Emphasis Panel (SRC (JJ))
Project Start
1991-03-04
Project End
1994-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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