The experimental model proposed in this study is designed to resolve fundamental questions concerning the existance of functional subsets among resident pulmonary alveolar macrophages (PAM). The study will take advantage of the strontium-89 (89Sr) monocytopenic mouse model which provides for the analysis of resident PAM surface marker heterogeneity in the absence of contamination by emigrating monocyte-macrophage. The objective of this study is to establish the existance of PAM subsets among resident PAM populations, in the absence of monocytes, and to evaluate the ability of those subsets to selectively increase their cell numbers in response to inflammatory stimuli. PAM subset heterogeneity and proliferative activity will be compared and contrasted in normal, outbred mice and in genetically defective inbred strains of mice. Flow cytometry will be used to characterize the subset distribution of a variety of monoclonal antibodies (MABs) to epitopes on the surface of mononuclear phagocytes. 125I-MAB binding studies will measure the number of MABs/PAM while propidium iodide staining will be employed to evaluate the cell cycle times of PAM subsets by flow cytometry. Upon defining a battery of subset-specific MABs, subsets will be sorted by fluoresence activated cell sorting and the cell cycle times measured for each subset. ICR mice will be challenged in vivo, with Candida albicans, Corynebacterium parvum, Listeria monocytogenes, endotoxin, alpha interferon or with macrophage growth factor (CSF-1), and the effects of challenge on PAM subset surface markers and subset proliferation determined. Similar studies will be performed in C57B1/6bgbg, C3H/HeJ, C3H/HeN, PN, W/Wv, and SLSLd inbred mouse strains. The objective of this study is to determine if alterations in the expression of PAM subset surface epitopes correlate with changes in proliferative capacity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001819-03
Application #
3074096
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1987-08-01
Project End
1989-02-28
Budget Start
1988-08-01
Budget End
1989-02-28
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983