Beck-Speier Ingrid, Dayal Niru, Denzlinger Claudio, Haberl Christopher, Maier Konrad L, Ziesenis Axel, Heyder Joachim
GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, D-85764 Neuherberg, Munich, Germany.
Prostaglandins Other Lipid Mediat. 2003 Jul;71(3-4):217-34. doi: 10.1016/s1098-8823(03)00041-8.
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.
近期研究表明，犬长期在体内暴露于中性硫（IV）/亚硫酸盐气溶胶会引发轻度炎症反应，而中性亚硫酸盐与酸性硫（VI）/硫酸盐气溶胶的组合所产生的影响则不那么明显。为了解其潜在机制，我们在体外研究了脂质介质在中性（pH 7）或中度酸性（pH 6）条件下肺泡巨噬细胞（AM）对硫相关化合物反应中的作用。在pH 7条件下与亚硫酸盐孵育的犬AM释放的血小板活化因子量比对照组高三倍（P < 0.005）。花生四烯酸、白三烯B4、5-羟基-二十碳四烯酸、前列腺素E2、血栓素B2和12-羟基十七碳三烯酸的生成增加了两倍（P < 0.0005）。然而，在pH 6条件下AM与亚硫酸盐孵育，或在pH 7或pH 6条件下与硫酸盐孵育后，这些代谢产物保持不变。在pH 7条件下，经亚硫酸盐处理的AM释放的介质刺激了中性粒细胞的呼吸爆发活性。分别用PD 98059抑制MAPK途径、用AACOCF3抑制胞质（cPLA2）和分泌型磷脂酶A2以及用硫醚酰胺-PC抑制后，可减少亚硫酸盐诱导的AM中类花生酸的形成。在pH 7条件下，亚硫酸盐使cPLA2活性增加了两倍。亚硫酸盐在磷脂代谢中刺激反应的这种机制表明，长期暴露于硫（IV）/亚硫酸盐与相当大的健康风险相关。
