Riise G C, Williams A, Kjellström C, Schersten H, Andersson B A, Kelly F J
Dept of Pulmonary Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Eur Respir J. 1998 Jul;12(1):82-8. doi: 10.1183/09031936.98.12010082.
Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.
闭塞性细支气管炎和不可逆性气道阻塞(如闭塞性细支气管炎综合征,BOS)的出现限制了肺移植受者的长期生存。本研究调查了BOS患者支气管肺泡灌洗(BAL)和经支气管活检(TBB)中炎症细胞及其活化标志物是否增加。还评估了BAL液中抗氧化剂的水平。将6名单肺移植、2名双侧肺移植和5名心肺移植且诊断为BOS的患者的BAL液和TBB与13名无BOS的移植受者进行比较。BAL液中髓过氧化物酶(MPO)、嗜酸性粒细胞阳离子蛋白(ECP)和白细胞介素(IL)-8的水平分别用作中性粒细胞和嗜酸性粒细胞活化及趋化的标志物。用抗MPO和ECP(EG2)的单克隆抗体对TBB进行免疫组织化学染色。发现BOS患者BAL中中性粒细胞百分比和MPO水平显著升高。这些发现与TBB中MPO的单克隆染色程度密切相关。BOS患者BAL中ECP和IL-8水平显著升高。BOS患者BAL中水溶性抗氧化剂抗坏血酸盐、尿酸盐和谷胱甘肽的浓度通常较低。结果表明,中性粒细胞浸润和活化以及氧化应激可能在闭塞性细支气管炎综合征的发生和/或进展中起作用。中性粒细胞活化标志物可能在监测该综合征患者的疾病活动方面具有潜在作用。