PMID- 26097236
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20160511
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 67
IP  - 10
DP  - 2015 Oct
TI  - Promotion of hypercoagulability in antineutrophil cytoplasmic antibody-associated 
      vasculitis by C5a-induced tissue factor-expressing microparticles and neutrophil 
      extracellular traps.
PG  - 2780-90
LID - 10.1002/art.39239 [doi]
AB  - OBJECTIVE: Patients with antineutrophil cytoplasmic antibody-associated 
      vasculitis (AAV) have a high frequency of venous thromboembolic events and a 
      hypercoagulable state. As C5a-primed neutrophils play an important role in the 
      development of AAV, we investigated whether C5a-induced neutrophil tissue factor 
      (TF)-expressing microparticles (MPs) and neutrophil extracellular traps (NETs) 
      might promote hypercoagulability in AAV. METHODS: TF-expressing MPs were measured 
      by flow cytometry. TF-expressing NETs were assessed by confocal microscopy. 
      Levels of thrombin-antithrombin complexes were determined by enzyme-linked 
      immunosorbent assay. The effect of C5a in sera from AAV patients was evaluated by 
      treating neutrophils with C5a receptor antagonist before incubation with sera 
      from AAV patients with active disease. RESULTS: Treatment of C5a-primed 
      neutrophils with antineutrophil cytoplasmic antibody (ANCA)-positive IgG resulted 
      in the release of TF-bearing MPs and NETs. Neutrophils from healthy donors 
      treated with sera from patients with active AAV released TF-bearing MPs and NETs, 
      which were abolished by treatment with C5a receptor antagonist. Involvement of TF 
      in MP- or NET-dependent thrombin generation was indicated by the findings of 
      antibody neutralization studies. NETs with thrombin-generating capacity were 
      demonstrated by DNase I treatment. CONCLUSION: C5a-primed neutrophils produce 
      TF-expressing MPs and NETs after stimulation with ANCAs, indicating a mechanism 
      for hypercoagulability in AAV that was not previously recognized.
CI  - (c) 2015, American College of Rheumatology.
FAU - Huang, Yi-Min
AU  - Huang YM
AD  - Peking University First Hospital and Peking University, Beijing, China.
FAU - Wang, Huan
AU  - Wang H
AD  - Peking University First Hospital and Peking University, Beijing, China.
FAU - Wang, Chen
AU  - Wang C
AD  - Peking University First Hospital and Peking University, Beijing, China.
FAU - Chen, Min
AU  - Chen M
AD  - Peking University First Hospital and Peking University, Beijing, China.
FAU - Zhao, Ming-Hui
AU  - Zhao MH
AD  - Peking University First Hospital and Peking University, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Nucleosomes)
RN  - 80295-54-1 (Complement C5a)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated 
      Vasculitis/*complications/physiopathology
MH  - Antibodies, Antineutrophil Cytoplasmic/pharmacology
MH  - Case-Control Studies
MH  - Cell-Derived Microparticles/*physiology
MH  - Cells, Cultured
MH  - Complement C5a/pharmacology/*physiology
MH  - Extracellular Traps/*physiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Microscopy, Confocal
MH  - Middle Aged
MH  - Neutrophils/drug effects/pathology/physiology
MH  - Nucleosomes/physiology
MH  - Thrombin/metabolism
MH  - Thrombophilia/*etiology/*physiopathology
MH  - Thromboplastin/*physiology
EDAT- 2015/06/23 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/06/23 06:00
PHST- 2014/07/02 00:00 [received]
PHST- 2015/05/28 00:00 [accepted]
PHST- 2015/06/23 06:00 [entrez]
PHST- 2015/06/23 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1002/art.39239 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2015 Oct;67(10):2780-90. doi: 10.1002/art.39239.