Effects of hypochlorite on cultured respiratory epithelial cells.
Neutrophils and eosinophils are involved in the pathogenesis of many respiratory diseases. The enzymes myeloperoxidase and eosinophil peroxidase catalyze the reaction of H2 O2 with Cl to produce the reactive oxygen species HOCl. Normal human bronchial epithelial (NHBE) cells were exposed to 0.18-0.90 mM HOCl for 48 h, and studied with immunohistochemical, metabolic and morphological studies. The ability of the cells to attach to each other and/or to the matrix was altered. Immunohistochemical studies showed a decreased amount of desmosomes and focal adhesion sites, although the morphology of the cells was not affected. The ability of the mitochondria to oxidize glucose was reduced. HOCl-exposed cells had an increased production of NO, probably by an increased activity of cNOS, due to increased intracellular Ca2+. The antioxidant N-acetylcysteine inhibited both the NO production and the effects of HOCl on glucose oxidation. The cNOS-inhibitor N-propyl-L-arginine inhibited HOCl-induced NO production. X-ray microanalysis showed an increase in the intracellular Na+ /K+ ratio, which indicates cell damage. In conclusion, exposure to HOCl results in cell detachment and metabolic alterations in normal human bronchial epithelial cells. Oxygen radicals could in part mediate the effects. Oxygen radicals could hence contribute to the observed epithelial damage in respiratory diseases.
Kampf
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Department of Medical Cell Biology, Uppsala University, Box 571, 751 23 Uppsala, Sweden. kampf@medcellbiol.uu.se
Roomans
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GM
D001980:Bronchi / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects; D004577:Electron Probe Microanalysis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D016596:Vinculin / Q000378:metabolism
D005609:Free Radicals; D016328:NF-kappa B; D009573:Nitrites; D016596:Vinculin; D006997:Hypochlorous Acid; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D005947:Glucose; D002118:Calcium