Martins M A, Pasquale C P, e Silva P M, Cordeiro R S, Vargaftig B B
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Int Arch Allergy Appl Immunol. 1990;92(4):416-24. doi: 10.1159/000235174.
Alterations in the local mast cell population and the eosinophil accumulation in the rat pleural cavity were studied using pleurisy induced by compound 48/80, a standard mast-cell-degranulating agent. Twenty-four hours after the intrathoracic injection of compound 48/80 (1-50 micrograms/cavity), a dose-dependent eosinophil enrichment of the exudate was noted, concomitantly with a drastic reduction in the total number of undamaged mast cells recovered from the pleural washing. At 24 h, neutrophil counts were not modified, and the number of mononuclear cells was increased, but only at the highest dose of compound 48/80. The temporal analysis showed that mast cell degranulation, exudation and neutrophil infiltration were maximal at the interval of 1-6 h after compound 48/80 (25 micrograms/cavity), whereas eosinophil accumulation peaked within 24 h, persisting elevated at least until 96 h. Since compound 48/80 was itself unable to induce eosinophil migration in vitro, attempts were made to investigate the potential involvement of recognized eosinophil chemo-attractants, such as histamine, leukotriene B4 (LTB4) and platelet-activating factor (PAF-acether). The intraperitoneal pretreatment with either cyproheptadine (2 mg/kg), meclizine (40 mg/kg), BW755C (25 mg/kg) or with the PAF-acether receptor antagonist WEB 2086 (20 mg/kg) had no effect on the eosinophil recruitment induced by compound 48/80 (25 micrograms/cavity). However, the treatment with the corticosteroid dexamethasone or the local inhibition of protein biosynthesis with cycloheximide (0.04-200 nmol/cavity) blocked the eosinophil pleural accumulation, but not the mast cell degranulation induced by compound 48/80. Our findings indicate that the pleural eosinophil accumulation induced by compound 48/80 is sensitive to dexamethasone, requires local protein biosynthesis and is independent of histamine, LTB4 and PAF-acether.
使用标准的肥大细胞脱颗粒剂化合物48/80诱导胸膜炎，研究大鼠胸腔内局部肥大细胞群的改变和嗜酸性粒细胞的积聚。在胸腔内注射化合物48/80（1 - 50微克/腔）24小时后，观察到渗出液中嗜酸性粒细胞呈剂量依赖性富集，同时从胸腔冲洗液中回收的未受损肥大细胞总数急剧减少。在24小时时，中性粒细胞计数未改变，单核细胞数量增加，但仅在化合物48/80的最高剂量时出现。时间分析表明，在化合物48/80（25微克/腔）注射后1 - 6小时内，肥大细胞脱颗粒、渗出和中性粒细胞浸润达到最大值，而嗜酸性粒细胞积聚在24小时内达到峰值，并至少持续升高至96小时。由于化合物48/80本身在体外不能诱导嗜酸性粒细胞迁移，因此尝试研究公认的嗜酸性粒细胞趋化因子如组胺、白三烯B4（LTB4）和血小板活化因子（PAF - 乙醚）的潜在作用。用赛庚啶（2毫克/千克）、美克洛嗪（40毫克/千克）、BW755C（25毫克/千克）或PAF - 乙醚受体拮抗剂WEB 2086（20毫克/千克）进行腹腔预处理，对化合物48/80（25微克/腔）诱导的嗜酸性粒细胞募集没有影响。然而，用皮质类固醇地塞米松治疗或用环己酰亚胺（0.04 - 200纳摩尔/腔）局部抑制蛋白质生物合成可阻断嗜酸性粒细胞在胸腔内的积聚，但不能阻断化合物48/80诱导的肥大细胞脱颗粒。我们的研究结果表明，化合物48/80诱导的胸腔嗜酸性粒细胞积聚对地塞米松敏感，需要局部蛋白质生物合成，并且与组胺、LTB4和PAF - 乙醚无关。
