Alveolar cells

In vitro studies on isolated cells including hepatocytes, erythrocytes, fibroblasts, and alveolar cells continue to demonstrate the specificity of action that these toxins have for liver cells (83,86,93). This specificity has led Aune and Berg (94) to use isolated rat hepatocytes as a screen for detecting hepatotoxic waterblooms of cyanobacteria. 

Large conductance CP-channels were described for renal epithelial cells such as MDCK-cells, urinary bladder, collecting duct and A6-cells [51-54] and in pulmonary alveolar cells [55]. 

More specifically, the blood-gas interface consists of the alveolar epithelium, capillary endothelium, and interstitium. The alveolar wall is made up of a single layer of flattened type I alveolar cells. The capillaries surrounding the alveoli also consist of a single layer of cells — endothelial cells. In between the alveolar epithelium and capillary endothelium is a very small amount of interstitium. Taken together, only 0.5 pm separates the air in the alveoli from the blood in the capillaries. The extreme thinness of the blood-gas interface further facilitates gas exchange by way of diffusion. 

Alveolar cell degeneration within 5 days LC80 (120 h) Alterations in alveolar macrophages... 

Shirasawa M, Fujiwara N, Hirabayashi S, Ohno H, Iida J, Makita K, Hata Y (2004) Receptor for advanced glycation end-products is a marker of type I lung alveolar cells. Genes Cells 9(2) 165-174... 

Dodoo AN, Bansal SS, Barlow DJ, Bennet F, Hider RC, Lansley AB, Lawrence MJ, Marriott C (2000) Use of alveolar cell monolayers of varying electrical resistance to measure pulmonary peptide transport. J Pharm Sci 89(2) 223-231... 

Poelma DL, Zimmermann LJ, van Cappellen WA, et al. Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro. Am J Physiol Lung Cell Mol Physiol 2004 287(5) L1056-L1065. 

Stephens et al have shown that, in rats, the degenerative changes in Type I alveolar cells occur after exposure to ozone at concentrations as low as 0.2 ppm for 3 h and that cells are replaced by Type II alveolar cells beginning a day after the exposure. With electron microscopy, Bils noted that the swelling of the epithelial alveolar lining cells of mice occurred after exposure to ozone at 0.6-1.3 ppm for 4 h. These changes... 

The effect of ozone on lysosomal enzymes has been studied by a number of investigators. Ozone has been clearly shown to inactivate lysozyme in vitro, but the effects of inhaled ozone on the activity of lysozyme appear to depend on the pulmonary fraction under study. Holzman et al. reported that exposure of rabbits or mice to ozone resulted in a decrease in the lysozyme activity of bronchopulmonary lavage samples. The effect was linearly related to product of ozone concentration and duration of exposure, although relatively high concentrations of ozone (2.0-S.S ppm) were used in this acute-exposure experiment (1-4 h). The authors also reported that alveolar cells present in the bronchial lavage of rabbits exposed to ozone at 10 ppm for 3 h had a decrease in the rate of lysosomal... 

Degenerative changes in Type 1 alveolar cells later replaced by Type II cells... 

The enzymatic degradation of insulin was also shown to occur in the cytosol of alveolar cells, the pH optimum of the proteases being 7.4 [38]. To what extent intracellular proteases play a significant role in limiting the absorption of insulin is not clear, since the size of insulin likely allows paracellular transport over the alveolar epithelium. However, for proteins of higher molecular weight, that require transcellular transport, these proteases might certainly limit bioavailability. 

In rats, inhalation of massive levels of y-alumina with an average particle size of 0.0005-0.04p for up to 285 days caused heavy desquamation of alveolar cells and secondary inflammation, but only slight evidence of fibrosis. The dust concentration in the exposure chamber was described as so high that visibility was reduced a few breaths of the atmosphere by the investigators caused bronchial irritation and persistent cough. 

These results show that retinyl esters in respiratory epithelium and in alveolar cells form a pool of vitamin A, which can be used physiologically by the tissue. The formation of retinol and at least RA from retinyl esters is strictly controlled. So far an unphysiological formation of RA and a subsequent toxicity seems not possible. Retinyl esters, however, are biochemically inert with respect to gene expression or vitamin A activity as long as they are not hydrolyzed. Consequently, the inhalative application, especially in cases of insufficient lung development, could represent a true alternative. The oral contribution is hardly successful because of the poor RBP s)mthesis of the liver and the lack of availability of a parenteral solution is currently not available. 

N02 is a relatively insoluble deep lung irritant capable of producing pulmonary edema. The type I cells of the alveoli appear to be the cells chiefly affected on acute exposure. At higher exposure, both type I and type II alveolar cells are damaged. Exposure to 25 ppm of N02 is irritating to some individuals 50 ppm is moderately irritating to the eyes and nose. Exposure... 

FI G U RE 10.2 Schematic representation of alveolar cells and possible mechanism of transport of molecules from the alveolar space into the circulation. Particles will release molecules of interest (gray circles) into the mucus in which the particle is embedded. The molecule can either be lost in the mucus, taken up by alveolar macrophages by phagocytosis or diffusion, taken up by alveolar epithelial cells by passive or active transport, or bypass the alveolar cells via paracellular transport depending upon the properties of the drug. Once a molecule has reached the extracellular space, the same mechanisms are possible for transport from the extracellular space into the blood. Molecules in the extracellular space may also reach to circulation via the lymph. 

Despite the fact that most of the alveolar surface is composited of alveolar epithelium, three primary types of cells are present in the alveoli type I alveolar cells, type II alveolar cells, and alveolar macrophages. Type I alveolar cells are also referred to as squamous pulmonary epithelial cells and are the continuous lining of the alveolar sac. Type II alveolar cells are also referred to as septal cells. Type II alveolar cells secrete the alveolar fluid that is necessary to keep the surface moist and to maintain surface tension of the alveolar fluid surface tension is necessary to keep the alveoli from collapsing. Alveolar fluid is a suitable environment for proteins when compared to the low pH and high protease levels associated with the intestine... 

Amato, P. A. and Loizzi, R. F. 1981. The identification and localization of actin and actin-like filaments in lactating guinea pig mammary gland alveolar cells. Cell Motility 1, 329-347. 

As a nonspecific fluid-phase endocytosis marker, HRP was used to evaluate the transport characteristics across rat alveolar epithelia cell monolayers. HRP was transported relatively intact (about 50%) across the alveolar barrier via nonspecific fluid-phase endocytosis. The permeability coefficient of HRP was decreased upon lowering the temperature [51], but after conjugation with transferrin via a disulfide linkage, HRP uptake by alveolar cell monolayers was significantly increased. Receptor-mediated internalization of the conjugated HRP was verified by competition for the transferrin receptor [52]. 

No data were located regarding the metabolites produced in humans or animals after either inhalation or dermal exposures to DEHP. Metabolism following these routes of exposure is expected to be similar to that after oral exposures, since there are lipases present in the alveolar cells of the lungs and the epidermis. However, the activities of these lipases are about 20% of that for the pancreatic esterase secreted into the intestines (Albro et al. 1987), so it is possible that a larger portion of an absorbed dose from respiratory or dermal exposures to DEHP will initially be presented to the tissues as unhydrolyzed DEHP rather than MEHP. 

In the A region the tight junction gap between type-I alveolar cells is reported as 1 nm. Other pores with equivalent radii of about 10 nm have also been identified. Consequently the permeability of the paracellular route is much greater than seen with other membranes. Large molecules up to 150 kDa are reported to be absorbed to a small extent into the bloodstream after pulmonary administration. 

MIC caused dose-dependent necrosis of brain cells and muscle cells (Anderson et al, 1988) of rats in culture these findings could explain neuromuscular complaints in Bhopal victims. Exposure of mice to 1-3 ppm MIC was found to inhibit erythroid precursors, pluripotent stem cells and granulocyte-macrophage progenitor recovery from this inhibitory effect was found within 3 weeks after 1 ppm but not after 3 ppm (Hong et al, 1987). At higher concentrations of 6-15 ppm, MIC inhibited cell cycling in bone marrow, alveolar cells, and T lymphocytes (Conner et al., 1987 Shelby et al, 1987) similar data were reported by others (Tice et al, 1987 Mason et al, 1987). MIC can inhibit bone marrow cell proliferation in mice (Meshram and Rao, 1988). MIC can cause necrosis in whole-brain cell cultures (Anderson et al, 1990) and inhibit differentiation in muscle cell cultures (Anderson et al, 1988). 

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