Impact of norepinephrine, dopamine and substance P on the activation and function of CD8 lymphocytes
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BioMed Central
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Meeting abstract
Impact of norepinephrine, dopamine and substance P on the activation and function of CD8 lymphocytes C Strell*, B Niggemann, KS Zaenker and F Entschladen Address: University Witten-Herdecke, Institut of Immunology, Germany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A88
doi:10.1186/1478-811X-7-S1-A88
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A88 © 2009 Strell et al; licensee BioMed Central Ltd.
During the past 30 years in became evident that neurotransmitter are important regulators of the immune system. The presence of nerve fibers and the release of neurotransmitters within lymphoid organs represents a mechanism by which signals from the central nervous system influence the immune cell functions. Neurotransmitter per se cannot induce any new function in immune cells but they are mainly responsible for the "fine-tuning" of an immune response. There is already a broad knowledge on the influence of neurotransmitter on B cells or CD4 lymphocytes/T helper cells, but with regard to CD8 positive cytotoxic T lymphocytes (CTLs) there are still many open questions. Therefore, we conducted the present study in order to complement the picture of neurotransmitter action on this leukocyte subset. We investigated the influence of norepinephrine, dopamine and substance P on the key functions of CTLs in vitro: activation, extravasation, migration and cytotoxicity. The activation of CTLs via CD3/CD28 cross-linking was inhibited by all of the three investigated neurotransmitters via mechanisms that involve PKA as investigated by the use of specific cAMP analoga. Furthermore, these cells showed a decrease in ERK1/2 phosphorylation and their level of IL-2 mRNA was reduced. Addition of high dose IL-2 was able to reverse the inhibiting effect of the neurotransmitters. With regard to extravasation we found dopamine to be a strong inducer of the adhesion of naïve CD8 lymphocytes to endothelium. In contrast, norepinephrine induced the adhesion of activated/effector T cells. Norepinephrine increases the IL-8 release from endothelium thereby leading to an increased adhesion of CXCR1 positive cells. We found CXCR1 to be mainly expressed on activated, per-
forin positive CTLs. All of the investigated neurotransmitter increased the spontaneous migratory activity of naïve CTLs with dopamine being the strongest inducer. But activated CTLs showed a reduced migratory activity in the presence of norepinephrine and substance P which seems to be mediated via the Epac/Rap1 pathwa
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