e Silva P M, Martins M A, Lima M C, Alves A C, Diaz B L, Cordeiro R S
Depto de Fisiologia e Farmacodinâmica, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brasil.
Int Arch Allergy Immunol. 1992;98(4):355-60. doi: 10.1159/000236211.
The intrathoracic injection of ovalbumin (12 micrograms/cavity) into actively sensitized rats led to a long-lasting eosinophil recruitment, which appeared 24 h after stimulation. In this study, pharmacological antagonists were used in order to evaluate the potential involvement of arachidonic acid metabolites and PAF-acether in the pleural eosinophil accumulation by antigen. Administration of the cyclooxygenase inhibitor indomethacin (2 mg/kg, i.p.), 1 h before the antigen challenge, failed to modify the 24-hour eosinophilia. In contrast, the dual cyclooxygenase and lipoxygenase inhibitor BW 755C and the more selective inhibitor BW A4C (5 and 10 micrograms/cavity, i.t.), injected 1 h before the antigen, were effective. Similarly, the PAF-acether antagonists BN 52021 and WEB 2086 (20 mg/kg, i.p.) abrogated the eosinophil accumulation, which was also sensitive to the topical treatment with the glucocorticoid dexamethasone (5 and 10 micrograms/cavity). Our findings suggest that the antigen-induced eosinophil mobilization is dependent on lipoxygenase derivatives and PAF-acether, but not on prostaglandins.
向主动致敏的大鼠胸腔内注射卵清蛋白(12微克/腔)会导致嗜酸性粒细胞长期募集,这种募集在刺激后24小时出现。在本研究中,使用药理学拮抗剂来评估花生四烯酸代谢产物和血小板活化因子(PAF-乙醚)在抗原诱导的胸膜嗜酸性粒细胞积聚中的潜在作用。在抗原攻击前1小时腹腔注射环氧化酶抑制剂吲哚美辛(2毫克/千克),未能改变24小时的嗜酸性粒细胞增多现象。相比之下,在抗原前1小时胸腔注射双环氧化酶和脂氧化酶抑制剂BW 755C以及更具选择性的抑制剂BW A4C(5和10微克/腔)是有效的。同样,PAF-乙醚拮抗剂BN 52021和WEB 2086(20毫克/千克,腹腔注射)消除了嗜酸性粒细胞的积聚,嗜酸性粒细胞积聚对糖皮质激素地塞米松(5和10微克/腔)的局部治疗也敏感。我们的研究结果表明,抗原诱导的嗜酸性粒细胞动员依赖于脂氧化酶衍生物和PAF-乙醚,而不是前列腺素。