Airborn particles of an infectious, industrial or environmental nature are constantly inhaled and must be cleared by lung defense mechanisms. Several mechanisms of clearance in man are suspected, usually from small animal experiments, and these may vary with species, the composition and size of particle, site of its deposition, presence of lung disease and particle load. The purpose of this study is to examine the routes of particle clearance from deposition sites distal to the muco-ciliary escalator (long term or """"""""alveolar"""""""" clearance) in an effort to quantify the lung clearance mechanisms under normal conditions in an animal model close anatomically and physiologically to man. For this purpose, we will use the sheep because of the resemblance of its lung in size and structure to man and because its size docility are consistent with highly desirable research methodology. Our approach will permit us to determine, in a quantitative manner, the routes of clearance of particles of 2 sizes (0.5 and 3 MICRO-CMD) after deposition in the """"""""alveolar"""""""" portion of the lung. The methods of assessing routes of particle clearance include 1) gamma camera imaging (for overall pattern and rate of clearance) in-vivo, and, in-vitro, after sacrifice and extirpation of the lung, 2) surveillance of routes of exists, such as a) whole lung lavage for the content of macrophage-related and unrelated particles, b) creation of tracheal stomae for collection and analysis of mucus for its particles and macrophages, c) lymph nodes for their radioactive content, reflecting particles, d) feces for total radioactive count reflecting particles eliminated through the airway, and 3) light microscopic corroboration of original sites of deposition and translocation during the course of clearance from extirpated lung tissue. In the process we should be able to quantify the portion of particles leaving alveoli by the tracheobronchial route (and the role of the macrophage therin), that portion clearing through the interstitium, and, of these, the fraction clearing through lymph nodes, and, finally, of the portion sequestered in the lung. We also shall determine how excess particle loads affect these avenues of clearance when given by inhalation as acute and chronic burdens of one to several orders of magnitude greater than control. This study thus reveal potential factors which lead to failure of the clearance system responsible for eliminating respired airborn particles from the alveolar surface of the lung and which may consequently aggravate their inflammatory and fibrogenic potential in the lung parenchyma.
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