Bozza P T, Castro-Faria-Neto H C, Martins M A, Larangeira A P, Perales J E, e Silva P M, Cordeiro R S
Departamento di Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
Eur J Pharmacol. 1993 Jun 1;248(1):41-7. doi: 10.1016/0926-6917(93)90023-j.
Intrathoracic injection of endotoxin lipopolysaccharide, LPS into rats induced a dose-dependent increase in the number of eosinophils recovered from the pleural cavity. The pleural eosinophil accumulation peaked within 24-48 h, and returned to basal levels within 120 h. This phenomenon was accompanied by mononuclear cell infiltration, and preceded by massive neutrophil accumulation. Pretreatment with indomethacin, BW 755C (a dual cyclo/lipoxygenase inhibitor), BW A4C (a specific lipoxygenase inhibitor) or the platelet activating factor (PAF) antagonists WEB 2086 and PCA 4248 failed to inhibit the endotoxin-induced pleural eosinophilia, whilst dexamethasone (5-10 micrograms/cavity) or cycloheximide (14-28 micrograms/cavity) abolished this phenomenon. Transfer of the cell-free pleural washing from LPS-treated donor rats to normal recipient rats led to a two-fold increase in the eosinophil counts. Treatment of donors, but not recipients, with cycloheximide or dexamethasone inhibited the eosinophil accumulation induced by the pleural washings, indicating that the generation of the eosinophilotactic activity, but not its effects, depends on protein synthesis. This eosinophilotactic activity was maintained after lyophilization and heating (100 degrees C for 30 min), but was destroyed by trypsin. This substance has a molecular weight ranging between 10 and 50 kDa. The available data suggest that the late eosinophil accumulation induced by LPS is independent of arachidonic acid metabolites and PAF, and probably depends on a newly generated heat-stable soluble protein.
向大鼠胸腔内注射内毒素脂多糖（LPS）可导致从胸腔回收的嗜酸性粒细胞数量呈剂量依赖性增加。胸腔嗜酸性粒细胞积聚在24 - 48小时内达到峰值，并在120小时内恢复到基础水平。这种现象伴有单核细胞浸润，并先有大量中性粒细胞积聚。用吲哚美辛、BW 755C（一种环氧化酶/脂氧化酶双重抑制剂）、BW A4C（一种特异性脂氧化酶抑制剂）或血小板活化因子（PAF）拮抗剂WEB 2086和PCA 4248进行预处理未能抑制内毒素诱导的胸腔嗜酸性粒细胞增多，而地塞米松（5 - 10微克/腔）或环己酰亚胺（14 - 28微克/腔）可消除这种现象。将LPS处理的供体大鼠的无细胞胸腔灌洗液转移至正常受体大鼠可导致嗜酸性粒细胞计数增加两倍。用环己酰亚胺或地塞米松处理供体而非受体可抑制胸腔灌洗液诱导的嗜酸性粒细胞积聚，这表明嗜酸性粒细胞趋化活性的产生而非其作用依赖于蛋白质合成。这种嗜酸性粒细胞趋化活性在冻干和加热（100℃ 30分钟）后仍能保持，但会被胰蛋白酶破坏。该物质的分子量在10至50 kDa之间。现有数据表明，LPS诱导的晚期嗜酸性粒细胞积聚与花生四烯酸代谢产物和PAF无关，可能依赖于一种新产生的热稳定可溶性蛋白。
