INCREASED 5-LIPOXYGENASE METABOLISM IN THE LUNGS OF HUMAN-SUBJECTS EXPOSED TO OZONE

The environmental pollutant ozone, at sufficiently high levels, is kno wn to induce pulmonary inflammation with resultant airway obstruction in normal subjects. Eicosanoids comprise one group of mediators releas ed from alveolar macrophages which are involved in the pathogenesis of inflammatory lung diseases. We compared the effects of 2-h exposures to 0.4 ppm ozone and filtered air on pulmonary function and eicosanoid levels in bronchoalveolar lavage fluid in 11 normal healthy volunteer s. Subjects were exposed to a 6-fold increase in minute ventilation us ing an adjusted work load on a cycle ergometer. All subjects complaine d of cough and dyspnea, and demonstrated increased ah-way obstruction, and increased specific airway resistance following ozone exposure as compared to air exposure. Bronchoalveolar lavage cell count demonstrat ed a 9-fold increase in the number of neutrophils with a lesser reduct ion in the number of alveolar macrophages following ozone exposure. No tably, bronchoalveolar ravage fluid leukotriene (LT) C-4(8-fold) and t o a lesser extent LTB(4) (1.5-fold) levels were higher following ozone exposure compared to air control, with no change in prostaglandins. I n a subset of four subjects, alveolar macrophage arachidonic acid meta bolism was studied in vitro following separate in vivo exposures to bo th ozone and air. Alveolar macrophages obtained following ozone exposu re released more 5-lipoxygenase (1.5-fold) metabolites, with no change in cyclooxygenase metabolites, than did cells obtained following air exposure. These observations document activation of the 5-lipoxygenase pathway in the lung following ozone exposure, and suggest that alveol ar macrophages may participate in the generation of LT, whose actions promote airway inflammation and obstruction.