Hypochlorous acid alters bronchial epithelial cell membrane properties and prevention by extracellular glutathione.
In chronic inflammatory diseases of the airways, such as cystic fibrosis, hypochlorous acid (HOCl) generated by neutrophils is involved in airway injury. We examined the effects of HOCl on 16HBE14o- bronchial epithelial cells by bolus addition or by generation with glucose oxidase plus myeloperoxidase. HOCl produced both carbonyl formation of a discreet number of proteins and modification of surface targets that were recognized by an antibody raised against HOCl-modified protein. Bolus or enzymatically generated HOCl decreased transepithelial resistance, but surprisingly bolus HOCl also increased short-circuit current. Glutathione in lung epithelial lining fluid is an excellent scavenger of HOCl; however, glutathione content is lower in cystic fibrosis epithelial lining fluid due to deficient glutathione transport to the apical side of bronchial-tracheal epithelial cells (Gao L, Kim KJ, Yankaskas JR, and Forman HJ. Am J Physiol Lung Cell Mol Physiol 277: L113-L118, 1999). We found that alteration of the GSH content of apical fluid above 16HBE14o- cells was protective because all HOCl-induced changes were delayed or eliminated by exogenous glutathione within the physiological range. Extrapolating this to cystic fibrosis suggests that HOCl can alter cell function without destruction but that elevating glutathione could be protective.
D001693:Biological Transport, Active / Q000187:drug effects; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000737:chemistry / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D011506:Proteins; D006997:Hypochlorous Acid; D005978:Glutathione