PMID- 29329391
OWN - NLM
STAT- MEDLINE
DCOM- 20190411
LR  - 20190411
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 30
IP  - 2
DP  - 2018 Mar 8
TI  - Oxidative burst and Dectin-1-triggered phagocytosis affected by norepinephrine 
      and endocannabinoids: implications for fungal clearance under stress.
PG  - 79-89
LID - 10.1093/intimm/dxy001 [doi]
AB  - A prolonged stress burden is known to hamper the efficiency of both the innate 
      and the adaptive immune systems and to attenuate the stress responses by the 
      catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate 
      immunity are the eradication of pathogens through phagocytosis and the 
      respiratory burst. We tested the concentration-dependent, spontaneous and 
      stimulated (via TNFalpha and N-formylmethionine-leucyl-phenylalanine) release of 
      reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) in 
      vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for 
      the EC receptor CB2. We evaluated phagocytosis of Dectin-1 ligating zymosan 
      particles and tested the cytokine response against Candida antigen in an in vitro 
      cytokine release assay. Increasing concentrations of NE did not affect 
      phagocytosis, yet stimulated ROS release was attenuated gradually reaching 
      maximum suppression at 500 nM. Adrenergic receptor (AR) mechanisms using 
      non-AR-selective (labetalol) as well as specific alpha-(prazosin) and beta-(propranolol) 
      receptor antagonists were tested. Results show that only labetalol and 
      propranolol were able to recuperate cytotoxicity in the presence of NE, 
      evidencing a beta-receptor-mediated effect. The CB2 agonist, AM1241, inhibited 
      phagocytosis at 10 microM and spontaneous peroxide release by PMNs. Use of the 
      inverse CB2 receptor agonist SR144528 led to partial recuperation of ROS 
      production, confirming the functional role of CB2. Additionally, AM1241 delayed 
      early activation of monocytes and induced suppression of IL-2 and IL-6 levels in 
      response to Candida via lower activity of mammalian target of rapamycin (mTOR). 
      These findings provide new insights into key mechanisms of innate immunity under 
      stressful conditions where ligands to the sympatho-adrenergic and EC system are 
      released.
FAU - Buchheim, Judith-Irina
AU  - Buchheim JI
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Hoskyns, Spencer
AU  - Hoskyns S
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
AD  - Centre of Human and Aerospace Physiological Sciences, Kings College London, UK.
FAU - Moser, Dominique
AU  - Moser D
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Han, Bing
AU  - Han B
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Deindl, Elisabeth
AU  - Deindl E
AD  - Walter-Brendel-Centre of Experimental Medicine (WBex), Germany.
FAU - Horl, Marion
AU  - Horl M
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Biere, Katharina
AU  - Biere K
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Feuerecker, Matthias
AU  - Feuerecker M
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Schelling, Gustav
AU  - Schelling G
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
FAU - Chouker, Alexander
AU  - Chouker A
AD  - Laboratory of Translational Research 'Stress and Immunity', Department of 
      Anaesthesiology, Hospital of the University of Munich, 
      Ludwig-Maximilians-University, Germany.
AD  - Centre of Human and Aerospace Physiological Sciences, Kings College London, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Endocannabinoids)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (dectin 1)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adult
MH  - Biomarkers
MH  - Cytokines/metabolism
MH  - Endocannabinoids/*pharmacology
MH  - Fungi/immunology
MH  - Granulocytes/drug effects/immunology/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Lectins, C-Type/*genetics
MH  - Leukocytes, Mononuclear/immunology/metabolism/microbiology
MH  - Mycoses/immunology/metabolism/microbiology
MH  - Norepinephrine/*pharmacology
MH  - Phagocytosis/*drug effects/*physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Respiratory Burst/*immunology
MH  - Stress, Physiological
MH  - Young Adult
EDAT- 2018/01/13 06:00
MHDA- 2019/04/12 06:00
CRDT- 2018/01/13 06:00
PHST- 2017/04/14 00:00 [received]
PHST- 2018/01/06 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2019/04/12 06:00 [medline]
PHST- 2018/01/13 06:00 [entrez]
AID - 4796934 [pii]
AID - 10.1093/intimm/dxy001 [doi]
PST - ppublish
SO  - Int Immunol. 2018 Mar 8;30(2):79-89. doi: 10.1093/intimm/dxy001.