Translocation of Particles from Pulmonary Alveoli into the Interstitium*

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Abstract
There is evidence that particulate matter deposited in the alveoli during inhalation can be translocated from the alveoli into the pulmonary interstitium. The translocated particles can stay in the interstitium or they can be further translocated into the lymphatics or possibly into the blood. We have evidence that ultrafine particles (∼20 nm) are interstitialized to a greater extent than larger particles of the same substance, and that the increased interstitial translocation is accompanied usually by an acute inflammatory response even after exposure to "nuisance" particles (e.g., TiO2, Al2O3, carbon black). Pulmonary lavage can be used to assess the content retained in the alveoli or in the pulmonary tissue per se. The hilar lymph node content is an additional indication of interstitial access and of the rate of the translocation. It seems that translocation is primarily correlated with the number and size of the particles, and the inflammatory response appears to scale with the surface area of the particles. An additional factor for interstitial access is the rate of dose delivery. The mechanisms involved in the translocation are not fully understood. We postulate that the phagocytosis of particles in the alveoli by AM counteracts their translocation toward the interstitium. There is morphological evidence that "free" particles are taken up by the type I alveolar epithelial cells, which would be the first step for interstitialization. The airway clearance pathway and the lymphatic system are interconnected at BALT sites, which may suggest particle clearance from the lymphatics towards the airways. The primary function of the alveolar particle clearance processes appears to be the maintenance of the thinness of the alveolo-capillary barrier by keeping on the alveolar side the alveolo-capillary barrier clean. Elucidation of these lung clearance pathways and associated processes is important toxicologically as well as for diagnostic or therapeutic use of aerosols in preferentially targeting certain pulmonary compartments.