In vivo nuclear magnetic resonance (NMR) exposes living tissue to large magnetic fields. Tissue constituents interact weakly with magnetic fields, and the direct effects of magnetic fields on cellular, biochemical, and genetic processes have not been reproducibly established. However, microscopic ferromagnetic particles be present as contaminants in the lungs and other organs. in many occupational settings, humans inhale magnetic-particle aerosols; a fraction of the particles are retained in the lungs and are ingested by pulmonary macrophages. Strong magnetic fields can cause these magnetic particles to move, rotate, and agglomerate. The toxicology of NMR fields on cells and tissues containing ferromagnetic particles is unknown. Years 01 and 02 of the project demonstrated that microscopic magnetic particles can be observed both optically and magnetically in cells. Moreover, such particles can serve as an experimental indicator of macrophage function by noninvasively providing information on the motions of cell organelles. We found that for phagocytized particles, cytoplasmic motions rotate particles and produce detectable changes in the magnetic field. In addition, intracellular particles can be twisted by an applied external field, which allows measurement of cytosol viscoelasticity. The proposed researeh will examine magnetie field effects on particle-containing lung macrophages. In years 04-06 we will address the following questions: (1) Can magnetic forces overcome the motile forces generated by the macrophage cytoplasm? Can magnetic forces restrain chemotaxis? We will quantify the magnitude of traction forces magnetometrically. (2) Can motion imposed by magnet fields on magnetic-particle containing cell organelles modulate the fusion of phagocytic and lysosomal vesicles? (3) Can alterations in cell organelle motions, magnetometrically detected, be used to identify the existence and activity of an intracellular infection (e.g., AIDS) in macrophages? The goal is to examine how phagocytized ferromagnetic particles modify cell function when cells are exposed to strong magnetic fields. At the same time, we will measure the forces generated in cell motility, we will examine the role of organelle motions in phagolysosome processing, and we will identify changes in motion and rheology caused by viral infection.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA040696-04
Application #
3180991
Study Section
(SSS)
Project Start
1985-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Dorries, A M; Valberg, P A (1992) Heterogeneity of phagocytosis for inhaled versus instilled material. Am Rev Respir Dis 146:831-7
Bizal, C L; Butler, J P; Feldman, H A et al. (1991) Kinetics of phagocytosis and phagosome-lysosome fusion in hamster lung and peritoneal macrophages. J Leukoc Biol 50:229-39
Bizal, C L; Butler, J P; Valberg, P A (1991) Viscoelastic and motile properties of hamster lung and peritoneal macrophages. J Leukoc Biol 50:240-51
Valberg, P A; Jensen, W A; Rose, R M (1990) Cell organelle motions in bronchoalveolar lavage macrophages from smokers and nonsmokers. Am Rev Respir Dis 141:1272-9
Reid, M B; Valberg, P A (1990) Intracellular oxidant production by isolated diaphragm. Chest 97:97S-98S
Zaner, K S; Valberg, P A (1989) Viscoelasticity of F-actin measured with magnetic microparticles. J Cell Biol 109:2233-43
Valberg, P A; Meyrick, B; Brain, J D et al. (1988) Phagocytic and motile properties of endothelial cells measured magnetometrically: effects of endotoxin. Tissue Cell 20:345-54
Valberg, P A; Butler, J P (1987) Magnetic particle motions within living cells. Physical theory and techniques. Biophys J 52:537-50
Valberg, P A; Feldman, H A (1987) Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys J 52:551-61