Magnetic particles retained in the lungs or in other organs can be detected from outside the body. Following inhalation or intratracheal instillation, as well as intravenous or intradermal injection, retained particles are magnetized by an external magnetic field. After this field is removed, the resulting magnetic field produced by the magnetized and aligned particles, called a remanent field, can be measured non-invasively by sensitive magnetometry. These measurements contain information about two phenomena: first, the progeressive decrease in the initial remanent field produced each time an animal is magnetized indicates clearance of the particules. Secondly, after magnetization, the remanent field decays during one half hour to as little as 10% of its initial value. This phenomenon is called relaxation and is caused by gradual random rotations of the particles away from their initial alignment. Over the past 3 years, we have assembled evidence from in vivo and in vitro experiments that the movement of particle-containing phagosomes and secondary lysosomes within macrophages is the major mechanism of relaxation. We have used non-invasive magnetometry to measure (1) the amount and distribution of particles in the body, (2) their clearance with time, (3) the motion of phagolysosomes, (4) cytoplasmic viscosity, and (5) the response of macrophages to various materials or conditions. These initial studies will be extended and several new ventures will be added. During the next five years, we propose to carry out these specific aims: (1) To correlate changes in magnetic particle relaxation and clearance with different types of lung injury; (2) To examine how the viscoelastic environment of particle containing organelles changes with time after particle deposition and with injury, (3) To use magnetometry to help elucidate the nature and importance of a newly discovered pulmonary macrophage - the intravascular pulmonary macrophage, (4) To use magnetometry to detect and quantify changes in the shape of alveoli, and (5) To use magnetometry to elucidate macrophage function and injury in other organs such as the liver and skin.
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