The proposed studies are designed to determine the role of alveolar macrophages in the regulation of pulmonary immune responses in normal humans and to further determine if alveolar macrophage regulation is altered in patients with diseases causing pulmonary fibrosis. We will investigate both how primary immune responses are induced to inspired or aspirated antigens and what mechanisms regulate immune effector mechanisms within the lung parenchyma once an individual has become immune. We will utilize normal human volunteers and patients with sarcoidosis and idiopathic pulmonary fibrosis to: 1) Determine whether alveolar macrophages from normal volunteers can stimulate antigen-specific responses by evaluating their ability to stimulate a secondary proliferative response in immune individuals, to trigger the release of lymphokines, and to stimulate a primary immune response in vitro, and by determining whether alveolar macrophages bear HLA-DR antigen and Mac-120 antigen; 2) Determine if alveolar macrophages from normal volunteers can deliver a second signal (Interleukin I) to activate lymphocytes by determining whether alveolar macrophages can stimulate a mitogen response and whether alveolar macrophages can produce IL-1; 3) Determine if alveolar macrophages from normal volunteers suppress immune responses by evaluating whether alveolar macrophages added to monocyte-dependent antigen-induced proliferative responses suppress proliferation and by further determining whether this suppression is mediated by soluble factors or by cell contact; 4) Determine whether AM from sarcoid patients and patients with IPF are more (or less) active in stimulating specific responses, producing Interleukin I or exhibiting suppression; 5) Determine whether pulmonary macrophages obtained from autospy from normal lungs are comparable in activity to AM obtained from bronchoalveolar washes from normal volunteers.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029543-04
Application #
3340669
Study Section
(SRC)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Nicod, L P; Lipscomb, M F; Toews, G B et al. (1989) Separation of potent and poorly functional human lung accessory cells based on autofluorescence. J Leukoc Biol 45:458-65

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