Neutrophils, unopposed neutrophil elastase, and alpha1-antiprotease defenses following human lung transplantation
Neutrophils, unopposed neutrophil elastase, and alpha1-antiprotease defenses following human lung transplantation
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DOI：
10.1164/ajrccm.164.1.2006096
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发表时间：
2001-07-01
影响因子：
24.7
通讯作者：
Love, RB
中科院分区：
文献类型：
--
作者：
Meyer, KC;Nunley, DR;Love, RB
中性粒细胞在再灌注后或感染、排斥和慢性移植物功能障碍时被隔离在新移植的肺中。由于释放到支气管肺泡分泌物中的无对抗性（游离）中性粒细胞弹性蛋白酶（NE）可能损伤肺同种异体移植物并损害细菌清除，我们评估了肺移植受者支气管肺泡分泌物中的总中性粒细胞数、髓过氧化物酶活性（作为中性粒细胞流入和脱粒的指标）、α（1）-抗蛋白酶（α（1）-AP）浓度和无对抗性NE活性。在因与α 1-AP缺乏相关的肺气肿而接受移植的受者以及没有这种缺乏的受者的支气管肺泡灌洗液（BALF）中，存在未对抗的NE活性（2，137支BALF中的171支; 8%）。17例α 1-AP缺乏的受者中有10例（59%）在移植后接受了至少1年的多次监测和诊断性支气管镜检查，至少有一个BALF含有未对抗NE，通常与大于或等于10（5）菌落形成单位/ml BALF的需氧菌相关。相反，58例肺气肿患者中有19例（33%）与α（1）-AP缺乏无关，32例囊性纤维化（CF）受者中有8例（25%），16例特发性肺纤维化（IPF）受者中有6例（38%），36例其他移植适应症受者中有11例（31%）BALF中无对抗NE。α 1-AP水平在移植后早期显著升高，在α 1-AP缺乏的受者中，随着感染或排斥反应的发生，α 1-AP水平显著升高。我们的研究结果表明，无对抗NE活性可以发现在两个α（1）-AP缺乏和α（1）-AP足够的受体移植后，通常与支气管内细菌感染。
Neutrophils are sequestered in the newly transplanted lung after reperfusion or with infection, rejection, and chronic graft dysfunction. Because unopposed (free) neutrophil elastase (NE) released into bronchoalveolar secretions may injure the lung allograft and impair bacterial clearance, we assessed total neutrophil numbers, myeloperoxidase activity as an index of neutrophil influx and degranulation, alpha(1)-antiprotease (alpha (1)-AP) concentrations, and unopposed NE activity in bronchoalveolar secretions from luna transplant recipients. Unopposed NE activity was present in bronchoalveolar lavage fluid (BALF) from recipients transplanted for emphysema associated with alpha (1)-AP deficiency as well as recipients without such deficiency (171 of 2,137 BALF; 8%). Ten of 17 (59%) recipients with alpha (1)-AP deficiency who were followed for at least 1 yr after transplant with multiple surveillance and diagnostic bronchoscopies had at least one BALF containing unopposed NE, usually associated with the presence of greater than or equal to 10(5) colony forming units/ml BALF of aerobic bacteria. In contrast, 19 of 58 (33%) with emphysema not associated with alpha (1)-AP deficiency, 8 of 32 (25%) recipients with cystic fibrosis (CF), 6 of 16 (38%) with idiopathic pulmonary fibrosis (IPF), and 11 of 36 (31%) with other indications for transplant had unopposed NE in BALF. alpha (1)-AP levels were significantly elevated in the early posttransplant time period and could be augmented considerably in alpha (1)-AP-deficient recipients with episodes of infection or rejection. Our findings indicate that unopposed NE activity can be found in both alpha (1)-AP-deficient and alpha (1)-AP-sufficient recipients after transplantation, usually in association with endobronchial bacterial infection.