Lapa e Silva J R, Ruffié C, Vargaftig B B, Pretolani M
Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
Eur Respir J. 1995 Aug;8(8):1321-7. doi: 10.1183/09031936.95.08081321.
Guinea-pigs sensitized by a subcutaneous injection of ovalbumin in Al(OH)3 and boosted 2 weeks later exhibit marked bronchial hyperresponsiveness to various agonists and intense bronchial wall infiltration by CD4+ T-lymphocytes and eosinophils. We have compared the effect of FK506, a novel immunosuppressive agent, on the mucosal infiltration by T-cells and eosinophils with the well established drugs, nedocromil sodium and dexamethasone. Sensitized Hartley guinea-pigs were treated subcutaneously for 5 days with FK506 (100 micrograms.kg-1 daily), nedocromil sodium (30 micrograms.kg-1 daily), or dexamethasone (200 micrograms.kg-1 daily). On the day of the experiment, i.e. one week after the booster injection of antigen, the animals were killed, the lungs dissected, frozen and cryostat sections stained by immunohistochemical methods using monoclonal antibodies specific for total T-lymphocytes, CD4+ and CD8+ T-cells. Cyanide-resistant eosinophil peroxidase activity was used to stain the eosinophils. Sections were coded and positive cells enumerated in the lamina propria and adventitia of the bronchi. Sensitized and antigen-stimulated vehicle-treated guinea-pigs showed marked infiltration of the bronchial wall by CD4+ T-lymphocytes and eosinophils compared with sensitized, non-antigen stimulated animals. As compared to vehicle, FK506 or dexamethasone abolished the T-cell/eosinophil invasion in the bronchial wall, whereas nedocromil sodium was ineffective in protecting the lungs from T-lymphocyte or eosinophil infiltration. We conclude that both FK506 and dexamethasone are effective in curtailing bronchial inflammation in allergic guinea-pigs, whereas nedocromil sodium did not resolve the inflammation associated with T-lymphocytes or eosinophils.
通过皮下注射卵清蛋白于氢氧化铝中致敏并在2周后加强免疫的豚鼠，对各种激动剂表现出明显的支气管高反应性，并且支气管壁有大量CD4 + T淋巴细胞和嗜酸性粒细胞浸润。我们比较了新型免疫抑制剂FK506与已确立的药物奈多罗米钠和地塞米松对T细胞和嗜酸性粒细胞黏膜浸润的影响。将致敏的Hartley豚鼠皮下注射FK506（每日100微克·千克-1）、奈多罗米钠（每日30微克·千克-1）或地塞米松（每日200微克·千克-1），持续5天。在实验当天，即抗原加强注射一周后，处死动物，解剖取出肺脏，冷冻后用免疫组织化学方法，使用针对总T淋巴细胞、CD4 +和CD8 + T细胞的单克隆抗体对冰冻切片进行染色。用抗氰化物的嗜酸性粒细胞过氧化物酶活性来染色嗜酸性粒细胞。对切片进行编码，并对支气管固有层和外膜中的阳性细胞进行计数。与致敏但未接受抗原刺激的动物相比，致敏并接受抗原刺激的溶媒处理豚鼠的支气管壁有明显的CD4 + T淋巴细胞和嗜酸性粒细胞浸润。与溶媒相比，FK506或地塞米松消除了支气管壁中的T细胞/嗜酸性粒细胞浸润，而奈多罗米钠在保护肺脏免受T淋巴细胞或嗜酸性粒细胞浸润方面无效。我们得出结论，FK506和地塞米松在减轻过敏性豚鼠的支气管炎症方面均有效，而奈多罗米钠不能消除与T淋巴细胞或嗜酸性粒细胞相关的炎症。
