PMID- 24831032
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 5
DP  - 2014
TI  - New aspects on the structure of neutrophil extracellular traps from chronic 
      obstructive pulmonary disease and in vitro generation.
PG  - e97784
LID - 10.1371/journal.pone.0097784 [doi]
LID - e97784
AB  - Polymorphonuclear neutrophils have in recent years attracted new attention due to 
      their ability to release neutrophil extracellular traps (NETs). These web-like 
      extracellular structures deriving from nuclear chromatin have been depicted in 
      ambiguous roles between antimicrobial defence and host tissue damage. NETs 
      consist of DNA strands of varying thickness and are decorated with microbicidal 
      and cytotoxic proteins. Their principal structure has in recent years been 
      characterised at molecular and ultrastructural levels but many features that are 
      of direct relevance to cytotoxicity are still incompletely understood. These 
      include the extent of chromatin decondensation during NET formation and the 
      relative amounts and spatial distribution of the microbicidal components within 
      the NET. In the present work, we analyse the structure of NETs found in induced 
      sputum of patients with acutely exacerbated chronic obstructive pulmonary disease 
      (COPD) using confocal laser microscopy and electron microscopy. In vitro induced 
      NETs from human neutrophils serve for purposes of comparison and extended 
      analysis of NET structure. Results demonstrate that COPD sputa are characterised 
      by the pronounced presence of NETs and NETotic neutrophils. We provide new 
      evidence that chromatin decondensation during NETosis is most extensive and 
      generates substantial amounts of double-helix DNA in 'beads-on-a-string' 
      conformation. New information is also presented on the abundance and location of 
      neutrophil elastase (NE) and citrullinated histone H3 (citH3). NE occurs in high 
      densities in nearly all non-fibrous constituents of the NETs while citH3 is much 
      less abundant. We conclude from the results that (i) NETosis is an integral part 
      of COPD pathology; this is relevant to all future research on the etiology and 
      therapy of the disease; and that (ii) release of 'beads-on-a-string' DNA studded 
      with non-citrullinated histones is a common feature of in vivo NETosis; this is 
      of relevance to both the antimicrobial and the cytotoxic effects of NETs.
FAU - Obermayer, Astrid
AU  - Obermayer A
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria.
FAU - Stoiber, Walter
AU  - Stoiber W
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria.
FAU - Krautgartner, Wolf-Dietrich
AU  - Krautgartner WD
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria.
FAU - Klappacher, Michaela
AU  - Klappacher M
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria.
FAU - Kofler, Barbara
AU  - Kofler B
AD  - Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
FAU - Steinbacher, Peter
AU  - Steinbacher P
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria.
FAU - Vitkov, Ljubomir
AU  - Vitkov L
AD  - Department of Cell Biology, University of Salzburg, Salzburg, Austria; Clinic of 
      Operative Dentistry, Periodontology and Preventive Dentistry, Saarland 
      University, Homburg, Germany.
FAU - Grabcanovic-Musija, Fikreta
AU  - Grabcanovic-Musija F
AD  - University Clinic of Pneumology, Paracelsus Medical University, Salzburg, 
      Austria.
FAU - Studnicka, Michael
AU  - Studnicka M
AD  - University Clinic of Pneumology, Paracelsus Medical University, Salzburg, 
      Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Extracellular Traps/*physiology
MH  - Female
MH  - Humans
MH  - Immunity, Innate
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/*immunology/pathology
MH  - Pulmonary Disease, Chronic Obstructive/immunology/*pathology
MH  - Sputum/immunology
PMC - PMC4022649
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/05/17 06:00
MHDA- 2015/06/16 06:00
PMCR- 2014/05/15
CRDT- 2014/05/17 06:00
PHST- 2014/02/05 00:00 [received]
PHST- 2014/04/23 00:00 [accepted]
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2014/05/15 00:00 [pmc-release]
AID - PONE-D-14-05124 [pii]
AID - 10.1371/journal.pone.0097784 [doi]
PST - epublish
SO  - PLoS One. 2014 May 15;9(5):e97784. doi: 10.1371/journal.pone.0097784. eCollection 
      2014.