PMID- 33240874
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - Neutrophil Extracellular Traps Induce MCP-1 at the Culprit Site in ST-Segment 
      Elevation Myocardial Infarction.
PG  - 564169
LID - 10.3389/fcell.2020.564169 [doi]
LID - 564169
AB  - BACKGROUND: Leukocyte-mediated inflammation is crucial in ST-segment elevation 
      myocardial infarction (STEMI). We recently observed that neutrophil extracellular 
      traps (NETs) are increased at the culprit site, promoting activation and 
      differentiation of fibrocytes, cells with mesenchymal and leukocytic properties. 
      Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 and 
      C-C chemokine receptor type 2 (CCR2). We investigated the interplay between NETs, 
      fibrocyte function, and MCP-1 in STEMI. METHODS: Culprit site and peripheral 
      blood samples of STEMI patients were drawn during primary percutaneous coronary 
      intervention. MCP-1 and the NET marker citrullinated histone H3 (citH3) were 
      measured by ELISA while double-stranded DNA was stained with a fluorescent dye. 
      The influence of MCP-1 on NET formation in vitro was assessed using isolated 
      healthy donor neutrophils. Human coronary artery endothelial cells (hCAECs) were 
      stimulated with isolated NETs, and MCP-1 gene expression was measured by ELISA 
      and qPCR. CCR2 expression of culprit site and peripheral blood fibrocytes was 
      characterized by flow cytometry. Healthy donor fibrocyte receptor expression and 
      chemotaxis were investigated in response to stimulation with MCP-1 and NETs in 
      vitro. RESULTS: NETs and concentrations of MCP-1 were increased at the culprit 
      site of 50 consecutive STEMI patients. NET stimulation of hCAECs induced 
      transcription of ICAM-1, IL-6, and MCP-1, and secretion of MCP-1. MCP-1 promoted 
      NET formation of healthy donor neutrophils in vitro. An increasing MCP-1 gradient 
      correlated with fibrocyte accumulation at the culprit site. Locally increased 
      MCP-1 levels were negatively correlated with CCR2 expression on fibrocytes. MCP-1 
      and NETs induced CCR2 downregulation on fibrocytes in vitro. NETs did not 
      function as a chemotactic stimulus for fibrocytes or monocytes and could block 
      migration in response to MCP-1 for both cell populations. CONCLUSION: NETs 
      function as signaling scaffolds at the culprit site of STEMI. NETs assist MCP-1 
      and ICAM-1 release from culprit site coronary artery endothelial cells. MCP-1 
      facilitates further NETosis. Monocytes enter the culprit site along an MCP-1 
      gradient, to transdifferentiate into fibrocytes in the presence of NETs.
CI  - Copyright (c) 2020 Hofbauer, Ondracek, Mangold, Scherz, Nechvile, Seidl, Brostjan 
      and Lang.
FAU - Hofbauer, Thomas M
AU  - Hofbauer TM
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Ondracek, Anna S
AU  - Ondracek AS
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Mangold, Andreas
AU  - Mangold A
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Scherz, Thomas
AU  - Scherz T
AD  - Department of Dermatology and Venereology, Landesklinikum Wiener Neustadt, Wiener 
      Neustadt, Austria.
FAU - Nechvile, Johanna
AU  - Nechvile J
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Seidl, Veronika
AU  - Seidl V
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Brostjan, Christine
AU  - Brostjan C
AD  - Department of Surgery, Division of Vascular Surgery and Surgical Research 
      Laboratories, Medical University of Vienna, Vienna, Austria.
FAU - Lang, Irene M
AU  - Lang IM
AD  - Department of Internal Medicine II, Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20201109
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7680894
OTO - NOTNLM
OT  - CCR2
OT  - ST-segment elevation myocardial infarction
OT  - fibrocytes
OT  - monocyte chemoattractant protein-1
OT  - neutrophil extracellular traps
EDAT- 2020/11/27 06:00
MHDA- 2020/11/27 06:01
PMCR- 2020/01/01
CRDT- 2020/11/26 05:48
PHST- 2020/05/20 00:00 [received]
PHST- 2020/10/08 00:00 [accepted]
PHST- 2020/11/26 05:48 [entrez]
PHST- 2020/11/27 06:00 [pubmed]
PHST- 2020/11/27 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.564169 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Nov 9;8:564169. doi: 10.3389/fcell.2020.564169. 
      eCollection 2020.