Lapa e Silva J R, Ruffié C, Lefort J, Nahori M A, Vargaftig B B, Pretolani M
Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
Mediators Inflamm. 1999;8(1):17-23. doi: 10.1080/09629359990676.
We examined the effect of the immunosuppressive agent, tacrolimus (FK506), on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL) fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumin-induced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing alpha4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue.
我们研究了免疫抑制剂他克莫司(FK506)对卵清蛋白激发的豚鼠抗原诱导的支气管对乙酰胆碱高反应性以及白细胞浸润气道的影响。在鼻内抗原激发前1小时和激发后5小时皮下注射0.5mg/kg的FK506,可预防支气管对雾化乙酰胆碱的高反应性、支气管肺泡灌洗(BAL)液和支气管组织中的嗜酸性粒细胞增多以及CD4 + T淋巴细胞对支气管壁的浸润。FK506还可抑制卵清蛋白诱导的黏附于肺血管内皮并表达α4整合素的白细胞数量增加。因此,FK506对致敏豚鼠抗原诱导的支气管高反应性的抑制作用可能与其预防气道炎症重要炎症成分出现的能力有关,如嗜酸性粒细胞聚集以及CD4 + T淋巴细胞浸润支气管组织。