PMID- 26700184
OWN - NLM
STAT- MEDLINE
DCOM- 20160817
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors 
      Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine 
      Levels.
PG  - e0145635
LID - 10.1371/journal.pone.0145635 [doi]
LID - e0145635
AB  - BACKGROUND: Acute stress drives a 'high-alert' response in the immune system. 
      Psychoactive drugs induce distinct stress hormone profiles, offering a 
      sought-after opportunity to dissect the in vivo immunological effects of acute 
      stress in humans. METHODS: 3,4-methylenedioxymethamphetamine (MDMA), 
      methylphenidate (MPH), or both, were administered to healthy volunteers in a 
      randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset 
      frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector 
      function were assessed, and linked to stress hormone levels and expression of 
      CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. RESULTS: MDMA/MPH 
      > MDMA > MPH robustly induced an epinephrine-dominant stress response. 
      Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets 
      towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, 
      but they expressed slightly reduced levels of the activating receptor NKG2D. 
      Preferential circulation of mature NK cells was associated with high epinephrine 
      receptor expression among this subset, as well as expression of integrin ligands 
      previously linked to epinephrine-induced endothelial detachment. CONCLUSION: The 
      acute epinephrine-induced stress response was characterized by rapid accumulation 
      of mature and functional NK cells in the peripheral circulation. This is in line 
      with studies using other acute stressors and supports the role of the acute 
      stress response in rapidly mobilizing the innate immune system to counteract 
      incoming threats.
FAU - Bigler, Marc B
AU  - Bigler MB
AD  - Translational Immunology, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
FAU - Egli, Simon B
AU  - Egli SB
AD  - Translational Immunology, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
FAU - Hysek, Cedric M
AU  - Hysek CM
AD  - Clinical Pharmacology, Dep. of Internal Medicine, University Hospital Basel, 
      Basel, Switzerland.
FAU - Hoenger, Gideon
AU  - Hoenger G
AD  - Immunobiology Lab, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
FAU - Schmied, Laurent
AU  - Schmied L
AD  - Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, 
      Basel, Switzerland.
FAU - Baldin, Fabian S
AU  - Baldin FS
AD  - Immunodeficiency Lab, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
FAU - Marquardsen, Florian A
AU  - Marquardsen FA
AD  - Immunodeficiency Lab, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
FAU - Recher, Mike
AU  - Recher M
AD  - Immunodeficiency Lab, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
AD  - Medical Outpatient Clinic, Dep. of Internal Medicine, University Hospital Basel, 
      Basel, Switzerland.
FAU - Liechti, Matthias E
AU  - Liechti ME
AD  - Clinical Pharmacology, Dep. of Internal Medicine, University Hospital Basel, 
      Basel, Switzerland.
FAU - Hess, Christoph
AU  - Hess C
AD  - Immunobiology Lab, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
AD  - Medical Outpatient Clinic, Dep. of Internal Medicine, University Hospital Basel, 
      Basel, Switzerland.
FAU - Berger, Christoph T
AU  - Berger CT
AD  - Translational Immunology, Dep. of Biomedicine, University Hospital Basel, Basel, 
      Switzerland.
AD  - Medical Outpatient Clinic, Dep. of Internal Medicine, University Hospital Basel, 
      Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20151223
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ADRB2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Receptors, Glucocorticoid)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Cells, Cultured
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Epinephrine/*blood
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunophenotyping
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Lymphocyte Subsets/*immunology/metabolism
MH  - Male
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Adrenergic, beta-2/genetics/*metabolism
MH  - Receptors, Glucocorticoid/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stress, Physiological/*immunology
PMC - PMC4689586
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/25 06:00
MHDA- 2016/08/18 06:00
PMCR- 2015/12/23
CRDT- 2015/12/25 06:00
PHST- 2015/08/21 00:00 [received]
PHST- 2015/12/07 00:00 [accepted]
PHST- 2015/12/25 06:00 [entrez]
PHST- 2015/12/25 06:00 [pubmed]
PHST- 2016/08/18 06:00 [medline]
PHST- 2015/12/23 00:00 [pmc-release]
AID - PONE-D-15-36848 [pii]
AID - 10.1371/journal.pone.0145635 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 23;10(12):e0145635. doi: 10.1371/journal.pone.0145635. 
      eCollection 2015.