Ozone-induced augmentation of eicosanoid metabolism in human nasal mucosa in vitro.
The increase in airway responsiveness induced by ozone exposure is associated with airway inflammation as evidenced by an increase in inflammatory mediators such as cyclooxygenase and lipoxygenase product formation found in bronchoalveolar lavage fluid, nasal lavage fluid and epithelial cell cultures. To examine eicosanoid metabolism after exposure to ozone, human nasal mucosa derived from 21 patients undergoing surgical therapy for chronic nasal obstruction was cultured with a specially designed in vitro organ culture device and exposed to 0.1 ppm ozone for 24 h. Eicosanoid formation was analyzed by the release of cyclooxygenase and lipoxygenase products into the culture supernatant (measured by enzyme immunoassay). Experiments revealed ozone-induced increases in cyclooxygenase and lipoxygenase product formation with significant increases in prostaglandin F2alpha (PGF2alpha), thromboxane B2 (TXB2) and leukotriene B4 (LTB4) (p<0.05). Moreover, we found an increase in the concentration of LTC4/D4/E4 in the supernatant of ozone-exposed mucosal samples, which however does not reach statistical significance. There was a significant correlation between PGF2alpha and TXB2 (r = 0.71, p<0.001). These results extend previous results from in vivo chamber studies suggesting that the mode of action of ozone is an oxidative reaction resulting in an increased activity of arachidonic acid metabolism in the airways with a subsequent increase in the concentration of cyclooxygenase and lipoxygenase products.
Schierhorn
K
K
Department of Clinical Immunology and Asthma OPD, Virchow-Klinikum, Humboldt University Berlin, Germany.
Zhang
M
M
Kacy
M
M
Kunkel
G
G
D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D011453:Prostaglandins / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
D015777:Eicosanoids; D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes; D010126:Ozone