PMID- 32829090
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20211204
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 88
DP  - 2020 Nov
TI  - Neutrophil extracellular traps promote corneal neovascularization-induced by 
      alkali burn.
PG  - 106902
LID - S1567-5769(20)31726-4 [pii]
LID - 10.1016/j.intimp.2020.106902 [doi]
AB  - OBJECTIVES: To investigate the effects of neutrophil extracellular traps (NETs) 
      on angiogenesis in vitro and in vivo and the regulatory role of mammalian target 
      of rapamycin (mTOR) activity in it. METHODS: The regulatory role of mTOR in NETs 
      formation was explored. In vitro, human neutrophils were pretreated with 
      rapamycin. NETs formation was measured using immunofluorescence staining of NETs 
      markers, SYTOX Green and PicoGreen after NaOH stimulation. In vivo, mice were 
      treated with rapamycin, and NETs formation in cornea was measured using 
      immunofluorescence staining 7 days after alkali burn. Then, the effects of NETs 
      on angiogenesis were investigated. In vitro, human neutrophils were treated with 
      DNase I or rapamycin. NETs were isolated after NaOH stimulation and the isolated 
      NETs were co-culture with human umbilical vein endothelial cells (HUVECs). HUVECs 
      migration, proliferation, and inflammatory activation were measured. In vivo, 
      mice were injected subconjunctivally with supernatant containing NETs. Corneal 
      neovascularization was visualized by immunofluorescence staining. RESULTS: NETs 
      structures can be observed in NaOH-stimulated neutrophils and alkali-burned mouse 
      cornea compared with normal group. Treated with rapamycin enhanced NETs formation 
      in response to NaOH management compared with DMSO control in vitro and in vivo. 
      NETs increased the migration, proliferation and inflammatory activation of 
      HUVECs, and subconjunctival injection of NETs promoted inflammatory and 
      angiogenic response in corneal alkali burn model. CONCLUSIONS: NETs formation can 
      be triggered by NaOH stimulation. mTOR activity has a negative regulatory effect 
      on NETs formation. NETs promoted angiogenic responses and inflammatory activation 
      of HUVECs and increased corneal neovascularization and inflammatory response.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Yuan, Kelan
AU  - Yuan K
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China. Electronic address: 
      yankeyuankelan@126.com.
FAU - Zheng, Jiao
AU  - Zheng J
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China.
FAU - Huang, Xiaodan
AU  - Huang X
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China.
FAU - Han, Yu
AU  - Han Y
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China.
FAU - Hu, Renjian
AU  - Hu R
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China.
FAU - Jin, Xiuming
AU  - Jin X
AD  - Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, 
      88 Jiefang Road, Hangzhou 310009, China. Electronic address: lzyjxm@zju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200820
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 55X04QC32I (Sodium Hydroxide)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Burns, Chemical/*pathology
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - *Corneal Neovascularization
MH  - Extracellular Traps
MH  - Eye Burns/*pathology
MH  - Human Umbilical Vein Endothelial Cells/physiology
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - *Neutrophils
MH  - Sodium Hydroxide
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - Corneal neovascularization
OT  - Mammalian target of rapamycin
OT  - NaOH
OT  - Neutrophil extracellular traps
OT  - Rapamycin
COIS- Declaration of interest The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper.
EDAT- 2020/08/24 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/24 06:00
PHST- 2020/05/27 00:00 [received]
PHST- 2020/08/12 00:00 [revised]
PHST- 2020/08/12 00:00 [accepted]
PHST- 2020/08/24 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/24 06:00 [entrez]
AID - S1567-5769(20)31726-4 [pii]
AID - 10.1016/j.intimp.2020.106902 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Nov;88:106902. doi: 10.1016/j.intimp.2020.106902. Epub 
      2020 Aug 20.