Particle Uptake and Translocation

The cytoskeleton appears to play an important role in transfer of mineral particles from the cell surface to the cell interior, and then in transport through the cell to the interstitium, but which cytoskeletal elements are involved in these processes are disputed issues. Moreover, there is some evidence that mineral particles can damage the cytoskeleton and such damage undoubtedly affects uptake. 

Very little is known of how these principles apply to uptake of mineral particles by tracheobronchial, bronchiolar, and type 1 and 11 cells. Cytochalasin treatment abolished uptake of crocidolite fibers by cultured pleural mesothelial 

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In ordinary phagocytic cells most, but not all, exogenous substances that become internalized are incorporated into lysosomes. To what extent this applies to mineral particles and pulmonary epithelial cells is uncertain. Morphological studies have shown incorporation of at least some short fibers of chrysotile and crocidolite, and of fine iron oxide and carbon particles (3,4,23,55,61,59,60, 73,149) into lysosomes, but other fibers, particularly long asbestos fibers, have been reported to reside in the cytoplasm, with no membranous structures surrounding them (58,61,147). 

In typical monolayer culture cells, lysosomes accumulate over time around the microtubule-organizing center near the nucleus, and disruption of microtubules with colchicine or nocodazole prevents this effect (149,150), whereas pacli-taxel (Taxol) makes perinuclear lysosome accumulation more prominent. Perinuclear accumulation of asbestos and other fibrous minerals has been seen in monolayer culture cells (149,151,152), and the transport of crocidolite fibers toward the nucleus of cultured newt lung is microtubule-mediated (149,153). This observation (149) really applies only to relatively short ( 5 lm) fibers that move in a saltatory fashion at a rate identical with non-fiber-containing lysosomes, whereas long fibers do not exhibit saltatory movements, perhaps because they are not enclosed within lysosomal membranes, or because their length produces contact with numerous microtubules and probably other cytoskeletal elements, and the fibers become enmeshed. 

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The use of nanoparticles for oral appHca-tion is an intensively studied concept for the delivery of poorly soluble drugs, as discussed above. Particle uptake has been known for more than 50 years via M-cells as specialized phagocytic enterocytes, but also via lymphoid tissue and normal intestinal enterocytes [75, 76]. The kinetics of particle uptake and translocation depend on biopharmaceutical parameters like accessibility through the mucus and contact with the enterocytes, as well as on the physical properties of the particle like its size, particle charge, surfactant coating and, sometimes, targeting devices. 

There are two possible sources of PCDD/Fs to vegetation the atmosphere and soil. Initially it was thought that PCDD/Fs would not be present in the atmosphere in quantities sufficient to contaminate plants owing to their low volatility, and early research in this area focused on uptake from soil. There are three possible pathways of soil-bound PCDD/Fs to aerial plant parts root uptake and translocation, volatilization followed by adsorption to foliage, and transfer of soil particles (see Figure 1). The first of these pathways has received the most attention. 

Most nanoparticle uptake and translocation research has quantified nanoparticles in vivo using some type of unique particle label. For example, nanoparticle laboratory studies have included radioactive particles [4], trace metals such as gold and iridium [7], and fluorescent particles [8]. However, the population exposures most relevant to health involve the emissions or deliberate release of high-production-volume manufactured nanomaterials and exposures to incidental nanoparticles, such as soot. Combustion emissions and manufactured powders such as fumed silica, ultraflne titanium dioxide (Ti02), and similar industrial materials rarely have a unique and easily detected label. 

Pappo, J., and Ermak, T. H., 1989, Uptake and translocation of fluorescent latex particles by rabbit Peyer s patch follicle epithelium A quantitative model for M cell uptake, Clin. Exp. Immunol. 76 144-148. 

A smaller size not only facilitates the cellular uptake and translocation of nanomaterials but also alters the interaction between nanomaterials and the cellular components. Changes in particle-protein interaction appear to influence silica nanomaterial-induced toxidty [69, 72, 74,80,102], as demonstrated in the pioneer studies reported in 2004 of the interaction between silica nanopartides and pro-... 

These observations suggest that, for any given dust, there are quite marked differences in particle uptake and interstitial translocation in the various portions of the airways and between the airways and alveoli. Also, there are probably differences in uptake of any given particle among the different airway and alveolar eptihelial cells. However, quantitative data on the magnitude of these differences are few. 

Jani PU, McCarthy DE, Florence AT. Titanium dioxide (rutile) particle uptake from the rat GI tract and translocation to systemic organs after oral administration. Int ] Pharm 1994 105(May 2) 157-168. 

Little information is available about differences in particle uptake as a function of either anatomical location within the lung or as a function of cell type. In the mouse, all types of conducting airway cells, except mucous cells, phagocytosed 5-nm-iron oxide particles administered by inhalation (72,73). The iron oxide particles were translocated through the cell to the interstitium, and this phenomenon appeared to occur primarily in ciliated cells. In human bronchial explants, the ciliated cells took up both asbestos and glass fibers (71), but uptake occurred primarily in areas with relatively few cilia, apparently because areas with numerous actively beating cilia tended to move particles away from the cell surfaces. In hamster tracheal explants, there was a similar effect for long, but not short, fibers of both chrysotile and crocidolite. 

Particle size it would appear that particles of certain compositions in the size range 50-3,000 nm are capable of uptake by the Peyer s patches and subsequent translocation through the lymphatics. Particles of 3-10 pm are often retained within the Peyer s patches and do not subsequently move through the lymph. Particles larger than 10 pm are generally not taken up by the GI tract. 

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