Abstract
BackgroundNeutrophils 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.MethodsIntegrity 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.ResultsNeutrophils 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.ConclusionsNeutrophils 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.
Highlights
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
Most neutrophils isolated from Bronchoalveolar lavage fluid (BALF) from non-transplanted subjects with cystic fibrosis (CF) (CF BALF) or from aspirated proximal airway secretions of lung transplant recipients (LTx Br Bronchial aspirate (Asp)) whose allografts had bacterial tracheobronchitis appeared swollen and had vacuoles in their cytoplasm
These changes were not observed in peripheral blood neutrophils taken from either healthy subjects (HS Peripheral blood (PB)) or from patients with lung transplant recipients (LTx PB)
Summary
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. Chronic lung disease in cystic fibrosis (CF) is characterized by bacterial infection and intense, neutrophildominated airway inflammation. The release of large amounts of neutrophil elastase by neutrophils as they undergo necrosis is thought to be a major cause of damage to epithelium and lung matrix that leads to diffuse bronchiectasis and bronchial obstruction [1,2,3,4]. If neutrophils undergo necrosis and are not ingested by tissue macrophages in a timely fashion, toxic constituents including proteases can be released from necrotic cells in an unregulated manner [5]. Neutrophil necrosis is probably the primary cause of airway and lung damage in the intensely inflamed CF lung [6,7,8,9], but little is known as to why the recruited neutrophils undergo necrosis, and there is no simple method that can identify neutrophils undergoing necrosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
