PMID- 32405324
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20220414
IS  - 1755-5922 (Electronic)
IS  - 1755-5914 (Print)
IS  - 1755-5914 (Linking)
VI  - 2020
DP  - 2020
TI  - Therapeutic Anticoagulation with Argatroban and Heparins Reduces Granulocyte 
      Migration: Possible Impact on ECLS-Therapy?
PG  - 9783630
LID - 10.1155/2020/9783630 [doi]
LID - 9783630
AB  - INTRODUCTION: Anticoagulants such as argatroban and heparins 
      (low-molecular-weight and unfractionated) play an immense role in preventing 
      thromboembolic complications in clinical practice. Nevertheless, they can also 
      have a negative effect on the immune system. This study is aimed at investigating 
      the influence of these substances on polymorphonuclear neutrophils (PMNs), whose 
      nonspecific defense mechanisms can promote thrombogenesis. METHODS: Blood samples 
      from 30 healthy volunteers were investigated, whereby PMNs were isolated by 
      density gradient centrifugation and incubated with 0.8 mug/mL of argatroban, 
      1.0 U/mL of low-molecular-weight heparin (LMWH), 1.0 U/mL of unfractionated 
      heparin (UFH), or without drug (control). A collagen-cell mixture was prepared 
      and filled into 3D mu-slide chemotaxis chambers (IBIDI(R) GmbH, Germany). 
      Stimulation was initiated by using a chemokine gradient of 
      n-formyl-methionine-leucyl-phenylalanine (fMLP), and microscopic observation was 
      conducted for 4.5 hours. The cells' track length and track straightness, as well 
      as the number of attracted granulocytes, level of ROS (reactive oxygen species) 
      production, and NET (neutrophil extracellular traps) formation, were analyzed and 
      categorized into migration distances and time periods. RESULTS: All three 
      anticoagulants led to significantly reduced PMN track lengths, with UFH having 
      the biggest impact. The number of tracks observed in the UFH group were 
      significantly reduced compared to the control group. Additionally, the UFH group 
      demonstrated a significantly lower track straightness compared to the control. 
      ROS production and NET formation were unaffected. CONCLUSION: Our data provide 
      evidence that anticoagulants have an inhibitory effect on the extent of PMN 
      migration and chemotactic migration efficiency, thus indicating their potential 
      immune-modulatory and prothrombotic effects.
CI  - Copyright (c) 2020 Andre Bredthauer et al.
FAU - Bredthauer, Andre
AU  - Bredthauer A
AUID- ORCID: 0000-0002-5779-7714
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Kopfmueller, Manuel
AU  - Kopfmueller M
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
AD  - Department of Internal Medicine II, Goldbergklinik Kelheim, Kelheim, Germany.
FAU - Gruber, Michael
AU  - Gruber M
AUID- ORCID: 0000-0002-5509-9760
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Pfaehler, Sophie-Marie
AU  - Pfaehler SM
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Lehle, Karla
AU  - Lehle K
AD  - Department of Cardiothoracic Surgery, University Medical Center Regensburg, 
      Regensburg, Germany.
FAU - Petermichl, Walter
AU  - Petermichl W
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Seyfried, Timo
AU  - Seyfried T
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Bitzinger, Diane
AU  - Bitzinger D
AUID- ORCID: 0000-0002-3080-9957
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
FAU - Redel, Andreas
AU  - Redel A
AD  - Department of Anesthesiology, University Medical Center Regensburg, Regensburg, 
      Germany.
AD  - Department of Anesthesiology, Klinikum St. Marien Amberg, Amberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200425
PL  - England
TA  - Cardiovasc Ther
JT  - Cardiovascular therapeutics
JID - 101319630
RN  - 0 (Anticoagulants)
RN  - 0 (Antithrombins)
RN  - 0 (Enoxaparin)
RN  - 0 (Pipecolic Acids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfonamides)
RN  - 94ZLA3W45F (Arginine)
RN  - IY90U61Z3S (argatroban)
SB  - IM
MH  - Adult
MH  - Anticoagulants/*adverse effects
MH  - Antithrombins/*adverse effects
MH  - Arginine/analogs & derivatives
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Enoxaparin/*adverse effects
MH  - Extracellular Traps/metabolism
MH  - Female
MH  - Granulocytes/*drug effects/immunology/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pipecolic Acids/*adverse effects
MH  - Reactive Oxygen Species/metabolism
MH  - Sulfonamides
MH  - Young Adult
PMC - PMC7196999
COIS- The authors declare that no conflict of interests exists.
EDAT- 2020/05/15 06:00
MHDA- 2020/07/07 06:00
PMCR- 2020/04/25
CRDT- 2020/05/15 06:00
PHST- 2020/01/06 00:00 [received]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/05/15 06:00 [entrez]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2020/04/25 00:00 [pmc-release]
AID - 10.1155/2020/9783630 [doi]
PST - epublish
SO  - Cardiovasc Ther. 2020 Apr 25;2020:9783630. doi: 10.1155/2020/9783630. eCollection 
      2020.