Increased expression of cyclooxygenase 2 mediates oil fly ash-induced lunginjury

We have previously shown that in vitro exposure to the combustion-derived a mbient air pollutant residual oil fly ash (ROFA) induces the expression of prostaglandin H synthase 2 (COX2) in human airway epithelial cells. To dete rmine the role of prostaglandins and COX2 expression in ROFA-induced lung i njury in vivo, we have examined the effect of intratracheal ROFA instillati on on COX2 expression, prostaglandin synthesis, and indices of pulmonary in jury and inflammation in adult Sprague-Dawley rats. ROFA treatment induced a marked increase in the level of prostagladin E-2 (PGE(2)) recovered in th e bronchoalveolar lavage fluid (BALF), which was effectively decreased by p retreating the animals with the specific COX2 inhibitor NS398. Immunohistoc hemical analyses of rat airways showed concomitant expression of COX2 in th e proximal airway epithelium of rats treated with ROFA. Increases in BALF p rotein, but not interleukin 6 (IL-6) increases or ROFA-induced polymorphonu clear neutrophils (PMN) influx into the airway, were blunted by administrat ion of NS398 prior to ROFA instillation. These data demonstrate that prosta glandins mediate lung injury induced by exposure to ROFA and implicate incr eased expression of COX2 ar a mechanism that contributes to the toxicity of metal-laden ambient particulate matter.