Sulfur-related air pollutants induce the generation of platelet-activating factor, 5-lipoxygenase- and cyclooxygenase-products in canine alveolar macrophages via activation of phospholipases A2.
Recent studies have shown that long-term in vivo exposure of dogs to neutral sulfur(IV)/sulfite aerosols induces mild inflammatory reactions, whereas the combination of neutral sulfite with acidic sulfur(VI)/sulfate aerosols evokes less pronounced effects. To understand underlying mechanisms, we studied in vitro the role of lipid mediators in the responses of alveolar macrophages (AMs) to sulfur-related compounds under neutral (pH 7) or moderate acidic (pH 6) conditions. Canine AMs incubated with sulfite at pH 7 released threefold higher amounts of platelet-activating factor than control (P < 0.005). Generation of arachidonic acid, leukotriene B4, 5-hydroxy-eicosatetraenoic acid, prostaglandin E2, thromboxane B2 and 12-hydroxyheptadecatrienoic acid increased twofold (P < 0.0005). However, these metabolites remained unchanged following incubation of AMs with sulfite at pH 6 or with sulfate at pH 7 or pH 6. Mediator release by sulfite-treated AMs at pH 7 stimulated respiratory burst activity of neutrophils. Inhibition of MAPK pathway by PD 98059, of cytosolic (cPLA2) and secretory phospholipases A2 by AACOCF3 and thioetheramide-PC, respectively, reduced sulfite-induced eicosanoid formation in AMs. Sulfite activated cPLA2 activity twofold at pH 7. This mechanism of sulfite-stimulated responses in phospholipid metabolism predicts that chronic exposure to sulfur(IV)/sulfite is associated with a considerable health risk.
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis / Q000096:biosynthesis*; D016718:Arachidonic Acid / Q000378:metabolism; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism; D007975:Leukotriene B4 / Q000032:analysis / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects*; D010741:Phospholipases A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000032:analysis / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D013431:Sulfates / Q000633:toxicity; D013447:Sulfites / Q000633:toxicity; D013455:Sulfur / Q000633:toxicity*; D013929:Thromboxane B2 / Q000032:analysis / Q000378:metabolism
D000393:Air Pollutants; D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D010972:Platelet Activating Factor; D013431:Sulfates; D013447:Sulfites; D007975:Leukotriene B4; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D013455:Sulfur; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D015232:Dinoprostone