Use of isolated lung cells in pulmonary toxicology

Nemery, Benoît; Hoet, Peter

doi:10.1016/0887-2333(93)90028-4

Cited by 9 publications

(2 citation statements)

References 48 publications

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“…The lung is a complex organ consisting of approximately 40 different cell types (Nemery and Hoet, 1993). This complex architecture reflects the physiological role of the lung as the gas exchange interface between the blood and the external environment.…”

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confidence: 99%

A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes

Somers¹,

Lindsay²,

Lowdon³

et al. 2007

Drug Metab Dispos

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ABSTRACT:The pulmonary and hepatic expression and catalytic activities of phase I and II drug-metabolizing enzymes were compared using human lung and liver tissue, and lung parenchymal cells (LPCs) and cryopreserved hepatocytes. Cytochrome P450 gene expression was generally lower in lung than in liver and CYP3A4 expression in lung was negligible. Esterase gene expression was similar in lung and liver. Expression of all sulfotransferase isoforms in lung was similar to or higher than that in liver. Lung tissue expressed low levels of UGT. However, the expression of UGT2A1 in lung was higher than that in liver. There was a range of catalytic activities in LPCs, including cytochrome P450, esterase, and sulfation pathways. Phase I activities were generally less than 10% of those determined in hepatocytes. Rates of ester hydrolysis and sulfation in LPCs were similar to those in hepatocytes. When measurable, glucuronidation in LPCs was present at very low levels, reflecting the gene expression data. The metabolism of salbutamol, formoterol, and budesonide was also investigated. Production of salbutamol-4-O-sulfate and budesonide oleate was observed in LPCs from at least two of three donor preparations studied. Formoterol sulfate and low levels of formoterol glucuronide were detected in one of three donors. In general, drug-metabolizing capability of LPCs is low compared with liver, although some evidence for substantial sulfation and deesterification capacity was observed. Therefore, these data support the use of this cell-based system for the investigation of key routes of xenobiotic metabolism in human lung parenchyma.

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confidence: 99%

A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes

Somers¹,

Lindsay²,

Lowdon³

et al. 2007

Drug Metab Dispos

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“…Bronchial epithelial cells, as well as bronchoalveolar macrophages, get rapidly into contact with particles administered by inhalation and are therefore susceptible to their effects (Nemery & Hoet, 1993). Furthermore, both cell types can produce and release chemokines and cytokines that play a central role both in the initiation of local inflammatory reactions and in the pathogenesis of asthma.…”

mentioning

confidence: 99%

Cytokine Profile of Human Bronchoalveolar Macrophages and Bronchial Epithelial Cells in Response to Inhalation Particles of the Cyclosporine Derivative Imm 125

Medina

1999

Inhalation Toxicology

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Administration of antiasthmatic drugs in the form of inhalation particles may alter the cytokine network in the airways, independently of their pharmacological actions. Changes induced by drugs not well tolerated may potentially contribute to the immunopathology of the disease, a strongly undesirable effect. In this study, cell viability assays and characterization of the cellular profile of cytokines and chemokines were performed in order to investigate the response of human bronchoalveolar macrophages and bronchial epithelial cells in culture to inhalation particles of the cyclosporine derivative IMM 125. Interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and IL-8 were assayed by enzyme-linked immunosorbent assay (ELISA) in the supernatants of bronchoalveolar macrophages, and RANTES, granulocyte--macrophage colony-stimulating factor (GM-CSF), and IL-8 in those of bronchial epithelial cells. Cells were studied both under basal and stimulated conditions (lipopolysaccharide and TNFalpha were used for activating macrophages and epithelial cells, respectively). The immunosuppressant FK 506 and the glucocorticoid Budesonide served as comparison. IMM 125 did not affect cell viability (except at high concentrations and long time periods). Moreover, IMM 125 did not induce an increase in the secretion of any of the cytokines and chemokines measured with respect to nontreated cells, except for a slight increase in IL-8, an effect that was also observed for FK 506, Budesonide, and inert latex particles, and was therefore regarded as nonspecific. Furthermore, IMM 125 significantly decreased the secretion of TNFalpha, IL-1beta by macrophages, and GM-CSF by epithelial cells, suggesting an antiinflammatory potential. In conclusion, the present in vitro results point to a good tolerance of human airways to IMM 125 inhalation particles.

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