Neutrophil necrosis and annexin 1 degradation associated with airway inflammation in lung transplant recipients with cystic fibrosis.
BACKGROUND
Neutrophils sequestered in lower respiratory tract secretions in the inflamed lung may undergo apoptosis and/or necrosis and release toxic cellular contents that can injure airways or parenchyma. This study examined the viability of neutrophils retrieved from the proximal airways of lung transplant recipients with bacterial tracheobronchitis.


METHODS
Integrity and stability of intracellular proteins in neutrophils from proximal airways and peripheral blood from lung transplant recipients with bacterial tracheobronchitis were analyzed via Western blot analysis and determination of neutrophil viability by morphologic appearance and flow cytometry.


RESULTS
Neutrophils in tracheobronchial secretions from lung transplant recipients with cystic fibrosis who had normal chest radiographic imaging but bronchoscopic evidence of purulent tracheobronchitis post-transplant were necrotic and associated with degradation of intracellular protein annexin 1. The neutrophil influx was compartmentalized to large airways and not detected in peripheral bronchoalveolar airspaces sampled via bronchoalveolar lavage. Peripheral blood neutrophils from healthy subjects cultured in vitro demonstrated that annexin 1 degradation, particularly to a 33 kDa annexin 1 breakdown product (A1-BP), was associated with neutrophil necrosis, but not apoptosis. Although annexin 1 degradation was not specific to neutrophil necrosis, it was a sensitive marker of intracellular protein degradation associated with neutrophil necrosis. Annexin 1 degradation to 33 kDa A1-BP was not observed in peripheral blood neutrophils from healthy subjects, but annexin 1 appeared to be degraded in peripheral blood neutrophils of lung transplant recipients despite a normal morphologic appearance of these cells.


CONCLUSIONS
Neutrophils were necrotic from the proximal airways of lung transplant recipients with bacterial tracheobronchitis, and this process may begin when neutrophils are still in the systemic circulation prior to sequestration in inflamed airways. Annexin 1 degradation to 33 kDa A1-BP may be useful as a sensitive marker to detect neutrophil necrosis.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Medical School, University of Wisconsin, Clinical Science Center, Madison, 53792-9988, USA.
Francis H C
FH
Tsao
Zhuzai
Z
Xiang
Adnan
A
Abbasi
Keith C
KC
Meyer
D000199:Actins / Q000378:metabolism; D017305:Annexin A1 / Q000378:metabolism*; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001991:Bronchitis / Q000378:metabolism* / Q000473:pathology*; D018893:Bronchoalveolar Lavage; D016022:Case-Control Studies; D002470:Cell Survival; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006801:Humans; D016040:Lung Transplantation; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D000199:Actins; D017305:Annexin A1; D015415:Biomarkers; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate