Direct evidence of secondary necrosis of neutrophils during intense lung inflammation.
Författare
Summary, in English
Several pulmonary inflammatory conditions are characterised by infiltration of neutrophils. Normally, neutrophils are silently removed by apoptosis, followed by phagocytosis. However, if phagocytosis fails, apoptotic cells undergo secondary necrosis. Recent findings of increased levels of the pan-necrosis marker lactate dehydrogenase in bronchoalveolar lavage from lipopolysaccharide-exposed mice implies potential involvement of secondary necrosis. Using a similar model, this study aimed to identify the source of lactate dehydrogenase and to search for direct histological evidence of secondary necrosis. Lipopolysaccharide (LPS) was administered to the lungs of BALB/c mice, and bronchoalveolar lavage and tissue samples were collected 4, 12, 24, 36, 48, 60 and 72 h after administration. LPS induced a patchy neutrophil-rich lung inflammation, where the numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive neutrophils were increased at 12 h and onwards. Lavage levels of neutrophils and lactate dehydrogenase increased significantly at 4 and 24 h, respectively. Detailed electron microscopic assessment of neutrophil activation and death modes revealed that up to 14% of the neutrophils were undergoing secondary necrosis, whereas apoptotic or primary necrotic structural cells were rarely found. In summary, this study provides direct evidence that secondary necrosis of neutrophils is a common process during intense lung inflammation. This implies that neutrophil apoptosis may cause rather than resolve airway inflammation.
Publiceringsår
2006
Språk
Engelska
Sidor
268-274
Publikation/Tidskrift/Serie
European Respiratory Journal
Volym
28
Issue
2
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
European Respiratory Society
Ämne
- Respiratory Medicine and Allergy
Nyckelord
- lactate dehydrogenase
- apoptosis
- neutrophils
- endotoxin
- inflammation
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1399-3003