The early involvement of pulmonary prostaglandins in hyperoxic lung injury.
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 greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha 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 PGs by BAL cells placed in cell 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-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .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 lipoxygenase 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology*; D008264:Macrophages / Q000502:physiology; D008854:Microscopy, Electron; D009504:Neutrophils / Q000502:physiology; D010100:Oxygen / Q000633:toxicity*; D011453:Prostaglandins / Q000097:blood / Q000502:physiology*; D011458:Prostaglandins E / Q000097:blood; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D007507:Therapeutic Irrigation; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D010100:Oxygen