Possible Mechanisms to Explain Dust Overloading of the Lungs

Possible Mechanisms to Explain Dust Overloading of the Lungs. MORROW, P. E. (1988). <it>Fundam. Appl. Toxicol</it>. 10, 369–384. This paper briefly reviews the available evidence on dust overloading of the lungs, a condition which has come to the forefront in many recently reported chronic inhalation studies. A general hypothesis is developed that dust overloading, which is typified by a progressive reduction of particle clearance from the deep lung, reflects a breakdown in alveolar macrophage (AM)-mediated dust removal due to the loss of AM mobility. The inability of the dust-laden AMs to translocate to the mucociliary escalator is correlated to an average composite particle volume per alveolar macrophage in the lung. When this paniculate volume exceeds approximately 60 μm3/AM, on the basis of a uniform distribution of particles over the AM pool size ({small tilde} 2.5 × 107 cells) in the Fischer 344 rat, the overload effect appears to be initiated. When the distributed paniculate volume exceeds {small tilde}600 μm3 per cell, the evidence suggests that AM-mediated particle clearance virtually ceases and agglomerated particle-laden macrophages remain in the alveolar region. This paper considers possible mechanisms why these particle-laden cells are immobilized, viz., one is based on excessive particle-cell, cell-cell chemotactic interactions, and migratory inhibition factors; the other considers the volumetric increase by phagocytized particles, per se, as leading to an inability of the AM to spread and migrate probably through a competitive requirement for surface membrane and cytoskeleton in both endocytotic and migratory functions.