title: Direct evidence of secondary necrosis of neutrophils during intense lung inflammation.
abstract: 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 labelling-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.
authors.affiliation: Dept of Experimental Medical Science, Division of Vascular and Airway Research, BMC D12, S-221 84 Lund, Sweden. Kristina.Rydell-Tormanen@med.lu.se
authors.forename: K
authors.initials: K
authors.lastname: Rydell-Törmänen
authors.forename: L
authors.initials: L
authors.lastname: Uller
authors.forename: J S
authors.initials: JS
authors.lastname: Erjefält
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000201:enzymology / Q000473:pathology; D018375:Neutrophil Activation; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000201:enzymology / Q000648:ultrastructure*; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*
chemical_list: D008070:Lipopolysaccharides; D007770:L-Lactate Dehydrogenase