Supramicron-sized particle clearance from alveoli: route and kinetics

Abstract

Particles inhaled and deposited in the alveoli of the lung, i.e., distal to the tracheobronchial mucociliary escalator, may theoretically be cleared by several routes, including solubilization, lymphatic drainage, and the mucociliary pathway. We studied the clearance routes and kinetics of an inert insoluble carbonized polystyrene particle of supramicron size (2.85 micron count median diameter) tagged with 57Co (half-life 270 days) in the adult unanesthetized sheep. The rate of particle clearance, assessed by gamma scintillation camera of the whole lung, showed a three-exponential function, comprising a rapid initial phase in the first 44 h of clearance for tracheobronchial deposition followed by a slower phase of mostly alveolar clearance in the next 30 days and a final phase of very slow relatively pure alveolar clearance. A balance study of particle route during clearance and autopsy of regional thoracic lymph nodes, blood, liver, and spleen demonstrated that this supramicron-sized particle cleared from alveoli predominantly via the mucociliary escalator of the tracheobronchial tree. Whole-lung lavage studies showed particle and macrophage recovery rates suggesting a sequestered state for alveolar-deposited particles, which may partly account for their slow clearance rates. The failure to find interstitial penetration by alveolar-deposited particles indicates that the macrophages engulfing these particles, at low particle burdens, travel normally in only one direction, i.e., from interstitium to alveolus and then to the mucociliary escalator.