Eicosanoid release from human bronchial epithelial cells upon exposure to toluene diisocyanate in vitro

✍ Scribed by Sabrina Mattoli; Mauro Masiero; Francesco Calabrò; Maurizio Mezzetti; Mario Plebani; Luigi Allegra

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 795 KB
• Volume: 142
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041420222

✦ Synopsis

Epithelial injury and inflammation are involved in airway hyperresponsiveness and asthma induced by toluene diisocyanate. In that isocyanates are insoluble and highly reactive c:ompounds, bronchial epithelial cells may represent the most important target cells of their toxic effect. We hypothesized that damage to airway epithelium by toluene diisocyanate may result in the release of metabolites of arachidonic acid, which are known to promote inflarnniation and to alter epithelial cell function and airway smooth muscle responsiveness. To test this hypothesis we examined eicosanoid products in the culture media of bronchial epithelial cells exposed in vitro to 8 and 18 ppb toluene diisocyanate. Epithelial cells derived from human bronchi obtained at surgery were cultured to confluency on collagencoated microporous membrane5. Those cells, which expressed differentiated characteristics of epithelial cells (they showed keratin-containing filaments and had a cobblestone appearance), were alternatively exposed to toluene diisocyanate or air for 30 min in a specially designed in vitro chamber. The production of metabolites of arachidonic acid was assessed by measuring the release of immunoreactive products into the cell medium at the end of the exposure and during a 2 hr period after exposure. This mehod revealed a predominant isocyanate-induced release of immunoreactive 15-hydroxyeicosatetraenoic acid. Release rate of this compound tended to be dose-related and was associated wilh cell darnage as asessed by the release of lactate dehydrogenase in the medium.