Pathways of clearance in mouse lungs exposed to iron oxide aerosols

Abstract

The history of particle clearance was studied in lungs of mice serially sacrificed at intervals up to 14 months following single exposures to an aerosol of submicronic, particulate, iron oxide used as a similitude for atmospheric dust. Clearance was followed by light microscopy in unstained and Prussian blue stained frozen and plastic embedded sections, as well as by electron microscopy, where iron oxide can be recognized by its form. Related problems were investigated through histochemical demonstration of acid phosphatase activity in pulmonary lysosomes and Prussian blue staining of various tissues after administration of iron compounds by gastrointestinal and vascular routes. The iron particles settle extensively but not uniformly on pulmonary alveolar surfaces. Clearance is centripetal and involves two mechanisms, an extracellular mechanism fed by fluid currents sweeping across the surfcace, and cellular mechanism principally involving alveolar macrophages. In the early post exposure period both actively remove deposited particles predominantly through the pulmonary airways. By 24 hours uncleared residues have become ingested and clearance thereafter results mainly from cellular action. Macrophages enter bronchial passages where they sometimes continue to pursue normal activities. A chronic phase of clearance begins when deposited particles become sequestered in macrophages of pulmonary connective tissues. These cells are reached by several routes, not least by crossing the bronchial epithelium. Particle clearance from these macrophages is very slow, and residue-containg cells eventually congregate in lymphoid tissues surrounding major bronchi. These findings are discussed as they help to develop an overall picture of clearance from the lungs and as they bear on related topics, such as functional roles of alveolar and pulmonary connective tissue macrophages and the pathogenesis of chronic bronchial disease.

Lymphatic removal of fluids and particles in the mammalian lung.

“…Once in the connective tissue compartment, which has a negative interstitial fluid pressure (28), the particles move toward the lymphatics and are subsequently removed by these vessels in a fashion similar to that in other regions of the body. The observation in the present study and those of other workers (24,29) suggest that particulate materials are able to cross the pulmonary epithelium within vesicles to gain entrance into the pulmonary interstitium. This removal of fluids and proteins from the pulmonary interstitium is similar to the pattern of lymphatic drainage in other tissue (27,30,31).…”

Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.

“…Most of the macrophages in the lung leave the alveoli by way of the airways and are expelled via the mucociliary pathway (19,37), but there are indications that PTM may leave the interstitium by way of the lymphatic channels (38,39) or perhaps the blood vessels (19), or travel locally to the bronchus-associated lymphoid tissue, where they might enter the airways at the level of the terminal bronchioli (40). Although our results do not provide any additional evidence for the proposed pathways of clearance, they do support the conclusion that there is no significant subpopulation of pulmonary macrophages having different kinetics, because such a subpopulation would have caused differences in labeling indices between the two populations in vivo.…”

Cellular Defences of the Lung: Comparative Perspectives

“…Spritzer et al, 1968) to be swallowed or expectorated; b) others move to the interstitium and either settle there or leave via the lymphatics (e.g. Sorokin and Brain, 1975). Compared to the PIMs, AMs have greater phagocytic activity and faster attachment and ingestion properties (Franke-Ullmann et al, 1996;Fathi et al, 2001).…”

“…In the bronchial tree, macrophages are suspended in the mucus carpet while others lie under the layer, directly attached onto the epithelial substratum (e.g. Sorokin and Brain, 1975;Brain et al, 1984;von Garnier and Nicod, 2009) (Fig. 34).…”