Neutrophils, unopposed neutrophil elastase, and alpha(1)-antiprotease defenses following human lung transplantation

Neutrophils are sequestered in the newly transplanted lung after reperfusio n or with infection, rejection, and chronic graft dysfunction. Because unop posed (free) neutrophil elastase (NE) released into bronchoalveolar secreti ons may injure the lung allograft and impair bacterial clearance, we assess ed total neutrophil numbers, myeloperoxidase activity as an index of neutro phil influx and degranulation, alpha(1)-antiprotease (alpha (1)-AP) concent rations, 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 defic iency who were followed for at least 1 yr after transplant with multiple su rveillance and diagnostic bronchoscopies had at least one BALF containing u nopposed 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 o f 32 (25%) recipients with cystic fibrosis (CF), 6 of 16 (38%) with idiopat hic pulmonary fibrosis (IPF), and 11 of 36 (31%) with other indications for transplant had unopposed NE in BALF. alpha (1)-AP levels were significantl y elevated in the early posttransplant time period and could be augmented c onsiderably in alpha (1)-AP-deficient recipients with episodes of infection or rejection. Our findings indicate that unopposed NE activity can be foun d in both alpha (1)-AP-deficient and alpha (1)-AP-sufficient recipients aft er transplantation, usually in association with endobronchial bacterial inf ection.