PMID- 27333499
OWN - NLM
STAT- MEDLINE
DCOM- 20170912
LR  - 20181202
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 43
IP  - 10
DP  - 2016 Oct
TI  - Iron-chelating agent, deferasirox, inhibits neutrophil activation and 
      extracellular trap formation.
PG  - 915-20
LID - 10.1111/1440-1681.12612 [doi]
AB  - Iron-chelating agents, which are frequently prescribed to transfusion-dependent 
      patients, have various useful biological effects in addition to chelation. 
      Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary 
      endothelial cell damage, which can lead to acute lung injury (ALI). We previously 
      reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol 
      myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced 
      ROS production in neutrophils, in vitro. Here, we investigate whether DFS 
      inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) 
      formation. Human neutrophils were incubated with DFS and stimulated with PMA or 
      fMLP. Human neutrophils were separated from heparinized peripheral blood using 
      density gradient centrifugation, and subsequently incubated with DFS. After 
      10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was 
      observed by electron microscopy. For observing NET formations using microscopes, 
      immunohistological analyses using citrullinated histone H3 and myeloperoxidase 
      antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were 
      conducted. NET formation was measured as the quantity of double-stranded DNA 
      (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 mumol/L) 
      inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 
      5-100 mumol/L concentration of DFS inhibited the release of dsDNA in a 
      dose-independent manner. We demonstrate that DFS inhibits not only ROS production 
      but also vacuolization and NET formation in neutrophils. These results suggest 
      the possibility of protective effects of DFS against NET-related adverse effects, 
      including ALI and thrombosis.
CI  - (c) 2016 John Wiley & Sons Australia, Ltd.
FAU - Kono, Mari
AU  - Kono M
AD  - Scientific Research, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
FAU - Saigo, Katsuyasu
AU  - Saigo K
AD  - Faculty of Pharmacological Sciences, Himeji Dokkyo University, Himeji, Japan.
FAU - Yamamoto, Shiori
AU  - Yamamoto S
AD  - Scientific Research, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
FAU - Shirai, Kohei
AU  - Shirai K
AD  - Faculty of Pharmacological Sciences, Himeji Dokkyo University, Himeji, Japan.
FAU - Iwamoto, Shuta
AU  - Iwamoto S
AD  - Faculty of Pharmacological Sciences, Himeji Dokkyo University, Himeji, Japan.
FAU - Uematsu, Tomoko
AU  - Uematsu T
AD  - Faculty of Pharmacological Sciences, Himeji Dokkyo University, Himeji, Japan.
FAU - Takahashi, Takayuki
AU  - Takahashi T
AD  - Department of Hematology, Shinko Hospital, Kobe, Japan.
FAU - Imoto, Shion
AU  - Imoto S
AD  - Department of Health Science, Kobe Tokiwa University, Kobe, Japan.
FAU - Hashimoto, Makoto
AU  - Hashimoto M
AD  - Kobe University Hospital, Kobe, Japan.
FAU - Minami, Yosuke
AU  - Minami Y
AD  - Kobe University Hospital, Kobe, Japan.
FAU - Wada, Atsushi
AU  - Wada A
AD  - Scientific Research, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
FAU - Takenokuchi, Mariko
AU  - Takenokuchi M
AD  - Faculty of Pharmacological Sciences, Himeji Dokkyo University, Himeji, Japan.
FAU - Kawano, Seiji
AU  - Kawano S
AD  - Kobe University Hospital, Kobe, Japan.
LA  - eng
PT  - Journal Article
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Benzoates)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Triazoles)
RN  - V8G4MOF2V9 (Deferasirox)
SB  - IM
MH  - Benzoates/*pharmacology
MH  - Cells, Cultured
MH  - Deferasirox
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Traps/*drug effects/metabolism
MH  - Humans
MH  - Iron Chelating Agents/*pharmacology
MH  - Neutrophil Activation/*drug effects/physiology
MH  - Phagocytosis/drug effects/physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Triazoles/*pharmacology
OTO - NOTNLM
OT  - iron chelators
OT  - morphology
OT  - neutrophils
EDAT- 2016/06/23 06:00
MHDA- 2017/09/13 06:00
CRDT- 2016/06/23 06:00
PHST- 2015/12/22 00:00 [received]
PHST- 2016/06/19 00:00 [revised]
PHST- 2016/06/20 00:00 [accepted]
PHST- 2016/06/23 06:00 [entrez]
PHST- 2016/06/23 06:00 [pubmed]
PHST- 2017/09/13 06:00 [medline]
AID - 10.1111/1440-1681.12612 [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2016 Oct;43(10):915-20. doi: 10.1111/1440-1681.12612.