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Resistance of rat pulmonary alveolar epithelial cells to neutrophil- and oxidant-induced injury.
Am J Respir Cell Mol Biol 1989; 1(3):221-9AJ

Abstract

We have previously reported that rat pulmonary alveolar epithelial cells are resistant to neutrophil-generated oxidants in contrast to the situation described for endothelial cells. In the present study, we investigated the roles of intracellular catalase and glutathione-dependent reactions in providing protection against cytotoxic concentrations of H2O2 and stimulated neutrophils. Catalase was found to be instrumental in protecting epithelial cells because when inhibited by either azide or 3-amino-1,2,4-triazole, there was an increase in the cytotoxic effect of exogenous H2O2 and stimulated neutrophils. Associated with this potentiation of injury was a reduction in epithelial cell clearance of H2O2. Partial inhibition of glutathione-dependent reactions by depleting intracellular glutathione with buthionine sulfoximine or by inhibiting the enzyme glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea also augmented the cytotoxic effect of both H2O2 and stimulated neutrophils. This increase in neutrophil-induced cytotoxicity was caused by the addition of an oxidant-dependent mechanism of killing on top of the previously described oxidant-independent pathway. Importantly, the increased susceptibility to injury caused by inhibition of glutathione-dependent reactions was not associated with a reduction in epithelial cell consumption of exogenous H2O2, contrary to the case with catalase. This suggests that there are glutathione-dependent reactions that protect epithelial cells in ways separate from reducing the total burden of exogenous H2O2 on the cells.

Authors+Show Affiliations

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2624761

Citation

Simon, R H., et al. "Resistance of Rat Pulmonary Alveolar Epithelial Cells to Neutrophil- and Oxidant-induced Injury." American Journal of Respiratory Cell and Molecular Biology, vol. 1, no. 3, 1989, pp. 221-9.
Simon RH, DeHart PD, Nadeau DM. Resistance of rat pulmonary alveolar epithelial cells to neutrophil- and oxidant-induced injury. Am J Respir Cell Mol Biol. 1989;1(3):221-9.
Simon, R. H., DeHart, P. D., & Nadeau, D. M. (1989). Resistance of rat pulmonary alveolar epithelial cells to neutrophil- and oxidant-induced injury. American Journal of Respiratory Cell and Molecular Biology, 1(3), pp. 221-9.
Simon RH, DeHart PD, Nadeau DM. Resistance of Rat Pulmonary Alveolar Epithelial Cells to Neutrophil- and Oxidant-induced Injury. Am J Respir Cell Mol Biol. 1989;1(3):221-9. PubMed PMID: 2624761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resistance of rat pulmonary alveolar epithelial cells to neutrophil- and oxidant-induced injury. AU - Simon,R H, AU - DeHart,P D, AU - Nadeau,D M, PY - 1989/9/1/pubmed PY - 1989/9/1/medline PY - 1989/9/1/entrez SP - 221 EP - 9 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 1 IS - 3 N2 - We have previously reported that rat pulmonary alveolar epithelial cells are resistant to neutrophil-generated oxidants in contrast to the situation described for endothelial cells. In the present study, we investigated the roles of intracellular catalase and glutathione-dependent reactions in providing protection against cytotoxic concentrations of H2O2 and stimulated neutrophils. Catalase was found to be instrumental in protecting epithelial cells because when inhibited by either azide or 3-amino-1,2,4-triazole, there was an increase in the cytotoxic effect of exogenous H2O2 and stimulated neutrophils. Associated with this potentiation of injury was a reduction in epithelial cell clearance of H2O2. Partial inhibition of glutathione-dependent reactions by depleting intracellular glutathione with buthionine sulfoximine or by inhibiting the enzyme glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea also augmented the cytotoxic effect of both H2O2 and stimulated neutrophils. This increase in neutrophil-induced cytotoxicity was caused by the addition of an oxidant-dependent mechanism of killing on top of the previously described oxidant-independent pathway. Importantly, the increased susceptibility to injury caused by inhibition of glutathione-dependent reactions was not associated with a reduction in epithelial cell consumption of exogenous H2O2, contrary to the case with catalase. This suggests that there are glutathione-dependent reactions that protect epithelial cells in ways separate from reducing the total burden of exogenous H2O2 on the cells. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/2624761/Resistance_of_rat_pulmonary_alveolar_epithelial_cells_to_neutrophil__and_oxidant_induced_injury_ L2 - http://www.atsjournals.org/doi/full/10.1165/ajrcmb/1.3.221?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -