The principal objectives of proposed research involve the quantitation and identification of routes of movement of protein macromolecules across the tracheobronchial epithelium. Utilizing principally horseradish peroxidase (HRP) (a glycoprotein of 40,000 daltons) as a tracer, movement of protein across tissue compartments will be measured with a radioimmunoassay for HRP and HRP localized in tissue by histochemical techniques and electron microscopy. We proposed to study the potential normal route(s) of movement of HRP across the epithelium, i.e., via pinocytotic vesicles, intercellular pathways, or specialized areas of passage, e.g., areas of rapid cellular turn-over or bronchus associated lymphoid tissue. In vivo and in vitro studies employing Ussing-like chambers will be employed in these studies. In a related investigation, the rate of antigen penetration through the epithlium employing 125I-HRP as a marker will be measured with reference to the sequence of respiratory events in acute allergic bronchoconstriction. As protein movements across the airway mucosa are likely bi-directional, route(s) of movement of macromolecules from interstitium to lumen, e.g., for IgG and HRP, will be investigated in in vitro studies. As mucosal permeability has been shown to increase in response to a variety of stimuli, potential mechanisms involved in regulating mucosal permeability, e.g., direct control by the epithelial cell itself, reflex (vagal) mechanisms, increased hydrostatic pressure resulting from edema, or liberated or activated enzymatic or permeability factors, will be investigated in in vivo and in vitro systems.
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