title: Acrolein: a potent modulator of lung macrophage arachidonic acid metabolism.
abstract: Resting rat pulmonary alveolar macrophages exposed to acrolein were stimulated to synthesize and release thromboxane B2 and prostaglandin E2 in a dose-dependent manner. Zymosan-activated pulmonary alveolar macrophages released approximately twice as much prostaglandin E2 as thromboxane B2, whereas acrolein-activated pulmonary alveolar macrophages released 4-5 times less prostaglandin E2 than thromboxane B2. In the zymosan-stimulated pulmonary alveolar macrophages, acrolein also induced a reversal in the relative amounts of prostaglandin E2 and thromboxane B2 synthesized and released into the culture medium. This reversal was achieved by a dose-dependent reduction in prostaglandin E2 synthesis. Although phagocytosis was also inhibited in a dose-dependent manner, the reduction in prostaglandin E2 appeared to be partially independent of particle ingestion since thromboxane B2 synthesis was not affected by low doses of acrolein. In fact, high doses induced a slight enhancement in thromboxane B2 synthesis. These results suggest that acrolein selectively inhibited the enzyme, prostaglandin endoperoxide E isomerase, necessary for the conversion of the endoperoxide to prostaglandin E2. Sulfhydryl reagents such as N-ethylmaleimide and 5,5'-dithiobis (2-nitrobenzoic acid) mimicked acrolein's effects, and reduced glutathione afforded protection against the effects of acrolein. These results indicated the possible involvement of acrolein's sulfhydryl reactivity in the inhibition of the isomerase enzyme. Propionaldehyde had no effect on macrophage arachidonic acid metabolism whereas crotonaldehyde mimicked the effects of acrolein. Pulmonary macrophages were unable to reverse the acrolein effects on arachidonate metabolite synthesis after 6 h in an acrolein-free environment. These data indicated the necessity of the unsaturated carbon bond for the acrolein effects on arachidonic acid metabolism and the relative irreversibility of acrolein's reaction with the macrophage.
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005260:Female; D008264:Macrophages / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D001095:Arachidonic Acids; D011458:Prostaglandins E; D013439:Sulfhydryl Reagents; D013931:Thromboxanes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000171:Acrolein; D015054:Zymosan; D015232:Dinoprostone