Channelpedia

PubMed 25477292


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav3.1 , Kv1.3 , SK4



Title: NMDA-receptor antagonists block B-cell function but foster IL-10 production in BCR/CD40-activated B cells.

Authors: Narasimhulu Simma, Tanima Bose, Sascha Kahlfuß, Judith Mankiewicz, Theresa Lowinus, Fred Lühder, Thomas Schüler, Burkhart Schraven, Martin Heine, Ursula Bommhardt

Journal, date & volume: Cell Commun. Signal, 2014 , 12, 75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25477292


Abstract
B cells are important effectors and regulators of adaptive and innate immune responses, inflammation and autoimmunity, for instance in anti-NMDA-receptor (NMDAR) encephalitis. Thus, pharmacological modulation of B-cell function could be an effective regimen in therapeutic strategies. Since the non-competitive NMDAR antagonist memantine is clinically applied to treat advanced Alzheimer`s disease and ketamine is supposed to improve the course of resistant depression, it is important to know how these drugs affect B-cell function.Non-competitive NMDAR antagonists impaired B-cell receptor (BCR)- and lipopolysaccharide (LPS)-induced B-cell proliferation, reduced B-cell migration towards the chemokines SDF-1α and CCL21 and downregulated IgM and IgG secretion. Mechanistically, these effects were mediated through a blockade of Kv1.3 and KCa3.1 potassium channels and resulted in an attenuated Ca(2+)-flux and activation of Erk1/2, Akt and NFATc1. Interestingly, NMDAR antagonist treatment increased the frequency of IL-10 producing B cells after BCR/CD40 stimulation.Non-competitive NMDAR antagonists attenuate BCR and Toll-like receptor 4 (TLR4) B-cell signaling and effector function and can foster IL-10 production. Consequently, NMDAR antagonists may be useful to target B cells in autoimmune diseases or pathological systemic inflammation. The drugs' additional side effects on B cells should be considered in treatments of neuronal disorders with NMDAR antagonists.