The goal of the proposed studies is to determine the molecular mechanisms controlling production of pulmonary macrophage derived products that facilitate opsonophagocytosis. Previous studies suggest a unique pattern of constitutive and regulated expression of several complement proteins in the alveolar macrophage. The importance of this cell in pulmonary host defenses and inflammatory lung disease provides the rationale for the proposed studies. Preliminary data coupled with the availability of relevant cDNA clones indicate the feasibility of the proposed studies. The transcriptional, translational and post- synthetic control of complement proteins (C1, C2, C4, factor B, C3), complement receptors (Crl, Cr3) and regulatory proteins (C1 inhibitor, factor I) will be examined in alveolar macrophages under resting conditions and following administration of endogenous (cytokines: IL-1, IFN gamma) and exogenous (endotoxin) mediators. Sub-populations of alveolar macrophages will be studied and compared to other mononuclear phagocytes with single cell and bulk assay systems. Functional and immunochemical methods will be used to monitor synthesis, Northern blot analysis to measure steady state specific mRNA concentration and nuclear """"""""run off"""""""" systems to study transcription. The long term objective of the proposed study is to define selective modulators of pulmonary macrophage function so as to limit tissue damage of inflammatory lung diseases without induction of a significant impairment of host defense against infection.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037591-04
Application #
3353389
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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