Perez S, Machado J, Cordeiro R, Martins M, Borojevic R, Silva P
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Manguinhos, Brazil.
Eur J Pharmacol. 1998 Sep 4;356(2-3):239-43. doi: 10.1016/s0014-2999(98)00541-x.
Platelet-activating factor (PAF) has been shown, in the rat model of pleural inflammation, to induce the generation of an intermediate proteic factor able to cause eosinophil proliferation in vitro. This study was undertaken to investigate the effect of the anti-mitotic compound doxorubicin on PAF-induced eosinophilia in rats, in order to evaluate the contribution of local cell proliferation to this phenomenon. The late eosinophil infiltration caused by another chemoattractant leukotriene B4 was used for comparison. We observed that local treatment with doxorubicin (20 and 40 microg/cavity), given 6 h after PAF (1 microg/cavity), suppressed the eosinophil accumulation within 24 h, whilst only the higher dose was effective when the drug was given 12 h post-PAF. An effect on chemotaxis was ruled out, since local doxorubicin (40 microg/cavity) failed to modify the eosinophil migration noted 24 h after leukotriene B4 (0.5 microg/cavity) and the neutrophil/eosinophil infiltration noted at 6 h after PAF injection. Transfer of the pleural fluids collected 6 h after PAF from donors to recipient rats caused significant eosinophil accumulation in the recipient rats, an effect which was inhibited by the co-administration of doxorubicin (40 microg/cavity). No inhibitory effect was noted when the drug was given 6 h after the pleural fluids were transferred. We also found no change in the number of blood or bone marrow eosinophils after PAF stimulation. We conclude that doxorubicin selectively impaired the late eosinophil accumulation triggered by PAF in the pleural cavity of rats, clearly indicating that local cell proliferation seems to contribute to the development of this inflammatory response.
在大鼠胸膜炎症模型中，血小板活化因子（PAF）已被证明可诱导一种中间蛋白因子的产生，该因子能够在体外引起嗜酸性粒细胞增殖。本研究旨在探讨抗有丝分裂化合物阿霉素对PAF诱导的大鼠嗜酸性粒细胞增多的影响，以评估局部细胞增殖对这一现象的作用。将由另一种趋化因子白三烯B4引起的晚期嗜酸性粒细胞浸润用作对照。我们观察到，在PAF（1微克/胸腔）注射6小时后给予阿霉素（20和40微克/胸腔）进行局部治疗，可在24小时内抑制嗜酸性粒细胞的积聚，而当在PAF注射后12小时给予药物时，只有较高剂量才有效。由于局部注射阿霉素（40微克/胸腔）未能改变在白三烯B4（0.5微克/胸腔）注射24小时后观察到的嗜酸性粒细胞迁移以及在PAF注射6小时后观察到的中性粒细胞/嗜酸性粒细胞浸润，因此排除了其对趋化作用的影响。将PAF注射6小时后收集的胸腔积液从供体转移至受体大鼠，可导致受体大鼠出现明显的嗜酸性粒细胞积聚，这一效应可被同时给予阿霉素（40微克/胸腔）所抑制。当在胸腔积液转移6小时后给予该药物时，未观察到抑制作用。我们还发现，PAF刺激后血液或骨髓中嗜酸性粒细胞的数量没有变化。我们得出结论，阿霉素选择性地削弱了PAF在大鼠胸腔中引发的晚期嗜酸性粒细胞积聚，这清楚地表明局部细胞增殖似乎有助于这种炎症反应的发展。
