title: Possible mechanisms to explain dust overloading of the lungs.
abstract: 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 particulate volume exceeds approximately 60 micron3/AM, on the basis of a uniform distribution of particles over the AM pool size (approximately 2.5 X 10(7) cells) in the Fischer 344 rat, the overload effect appears to be initiated. When the distributed particulate volume exceeds approximately 600 micron3 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.
authors.affiliation: Environmental Health Sciences Center, University of Rochester, School of Medicine and Dentistry, New York 14642.
authors.forename: P E
authors.initials: PE
authors.lastname: Morrow
mesh_terms: D000818:Animals; D004391:Dust / Q000009:adverse effects*; D006801:Humans; D008171:Lung Diseases / Q000503:physiopathology*; D009784:Occupational Diseases / Q000209:etiology / Q000503:physiopathology*
chemical_list: D004391:Dust