The proposal generally aims to develop a clear understanding of when and under what conditions pulmonary macrophages appear in prenatal lungs, what their antecedents are, what their capacity may be for respiratory defense, and how they relate to macrophage populations present in postnatal lungs. Stromal cells of the lungs are thought to provide a supportive microenvironment for macrophage development and will also be investigated. Current work has demonstrated the existence and ultrastructural appearance of a macrophage precursor in embryonic lung mesenchyme, designated CFU-rAM. The developmental potential of this cell is readily explored in lung organ cultures. Accordingly, plans are (1) to characterize CFU-rAM and its relationship to cells of macrophage lineage present in early embryos and older lungs; (2) to determine if its descendants are represented in the alveolar macrophage population of postnatal lungs; (3) to see if it may

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033070-10
Application #
3344663
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1984-07-01
Project End
1997-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Sorokin, S P; Hoyt Jr, R F; Reenstra, W R et al. (1997) Factors influencing fetal macrophage development: III. Immunocytochemical localization of cytokines and time-resolved expression of differentiation markers in organ-cultured rat lungs. Anat Rec 248:93-103
Sorokin, S P; Hoyt Jr, R F; McNelly, N A (1996) Factors influencing fetal macrophage development: I. Reactions of the tumor necrosis factor-alpha cascade and their inhibitors. Anat Rec 246:481-97
Sorokin, S P; McNelly, N A; Hoyt Jr, R F (1996) Factors influencing fetal macrophage development: II. Effects of the PDGF subfamily of protein-tyrosine kinase receptor ligands as studied in organ-cultured rat lungs. Anat Rec 246:498-506
Sorokin, S P; McNelly, N A; Hoyt Jr, R F (1994) Exogenous cytokines enhance survival of macrophages from organ cultured embryonic rat tissues. Anat Rec 240:398-406
Sorokin, S P; McNelly, N A; Hoyt Jr, R F et al. (1994) Precursors of macrophages in embryonic rat lungs fail to exhibit granulocyte-forming potential. Anat Rec 240:387-97
Sorokin, S P; McNelly, N A; Hoyt Jr, R F (1994) Early development of macrophages in intact and organ cultured hearts of rat embryos. Anat Rec 239:306-14
Sorokin, S P; McNelly, N A; Blunt, D G et al. (1992) Macrophage development: III. Transformation of pulmonary macrophages from precursors in fetal lungs and their later maturation in organ culture. Anat Rec 232:551-71
Sorokin, S P; McNelly, N A; Hoyt Jr, R F (1992) Macrophage development: IV. Effects of blood factors on macrophages from prenatal rat lung cultures. Anat Rec 233:415-28
Sorokin, S P; Hoyt Jr, R F (1992) Macrophage development: I. Rationale for using Griffonia simplicifolia isolectin B4 as a marker for the line. Anat Rec 232:520-6
Sorokin, S P; McNelly, N A; Hoyt Jr, R F (1992) CFU-rAM, the origin of lung macrophages, and the macrophage lineage. Am J Physiol 263:L299-307

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