To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role. we exposed adult rabbits to >95% )2 or air for 24, 40. 48. or 65 hours. At the end of each study, bronchoalveolar lavage (BALI of the left lung was performed. and the right lung was inflated and fixed for light and electron microscopy. PGE2. B-keto-PGF2α and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three POs by BAL cells placed in call culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours. as evidenced by significant increase in BAL total protein and percent PMNs. and by morphologic findings. At 40 hours. however, BAL fluid PGE2 and 6-keto-PGF2α increased and BAL cell production of all 3 POs was significantly increased (p<.05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or. rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygensse pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia.
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