Cyclooxygenase inhibition in lungs or in neutrophils attenuates neutrophil-dependent edema in rat lungs perfused with phorbol myristate acetate.
Results from previous studies indicate that injury in isolated rat lungs perfused with buffer containing phorbol myristate acetate (PMA) and rat neutrophils (PMNs) is dependent on the production of reactive oxygen species and thromboxane (Tx) A2. The purpose of this study was to determine whether the lung or the PMN was the source of TxA2 required to produce lung injury in this model. Prostanoid synthesis by rat lungs or PMNs was inhibited selectively by pretreatment of either rats or isolated PMNs with aspirin (100 mg/kg p.o. or 100 microM, respectively). Unbound aspirin was removed from the lungs and PMNs before use in experiments. Lungs from vehicle-pretreated rats that were perfused with PMA and untreated PMNs exhibited increases in weight, lavage fluid albumin content and TxB2 production with respect to lungs perfused with PMA but no PMNs. Increases in these markers were prevented when cyclooxygenase from either the lungs or the PMNs was inhibited. These results indicate that TxA2 is produced by both PMNs and by lung cells in this preparation, and that TxA2 production by both of these sources is required for the manifestation of edema.
Carpenter-Deyo
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Roth
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D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology* / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D010100:Oxygen