Müller M, Grunewald J, Olgart Höglund C, Dahlén B, Eklund A, Stridh H
Dept of Medicine, Division of Respiratory Medicine, Lung Research Laboratory, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Eur Respir J. 2006 Sep;28(3):513-22. doi: 10.1183/09031936.06.00118505. Epub 2006 May 31.
The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.
在哮喘反应期间气道中淋巴细胞数量的增加被认为是这些细胞募集增加的结果。然而，凋亡率降低也可能导致数量增加。本研究的目的是调查变应原气道激发是否会影响特应性哮喘患者肺和外周血淋巴细胞（PBL）的凋亡表型。来自12名哮喘患者的支气管肺泡灌洗（BAL）淋巴细胞和PBL，这些患者之前分别接受过变应原激发（n = 7）或生理盐水激发（n = 5），在体外将其暴露于凋亡刺激物三丁基锡（TBT）并检测凋亡情况。气道变应原激发导致BAL淋巴细胞对TBT诱导的凋亡敏感性降低，激发前凋亡细胞为42.2%（范围33.9 - 62.5%），激发后为23.5%（范围15.3 - 42.4%），而PBL未受影响。凋亡抗性增加与表达Bcl - 2的淋巴细胞数量增加相关。有趣的是，与存活的PBL相比，存活的BAL淋巴细胞中基线半胱天冬酶 - 3样活性显著升高，且不受变应原暴露的影响。总之，吸入变应原使支气管肺泡灌洗淋巴细胞对凋亡更具抗性，而外周血淋巴细胞完全未受影响，表明气道淋巴细胞的凋亡表型可能在哮喘炎症中起作用。
