• Immunobiology · Aug 2013

    Modulation of immune functions in polymorphonuclear neutrophils induced by physostigmine, but not neostigmine, independent of cholinergic neurons.

    • Diane I Bitzinger, York A Zausig, Christoph Paech, Michael Gruber, Hendrik Busse, Barbara Sinner, Bernhard M Graf, and Benedikt Trabold.
    • Department of Anaesthesiology, University of Regensburg, Regensburg, Germany. diane.bitzinger@ukr.de
    • Immunobiology. 2013 Aug 1;218(8):1049-54.

    BackgroundCholinesterase inhibitors (Ch-I) improve survival in experimental sepsis consistent with activation of the cholinergic-anti-inflammatory-pathway. So far, less is known about whether Ch-I have a direct immunomodulatory effect on immune cells (polymorphonuclear neutrophils, PMN) in the absence of cholinergic neurons. We investigated the concentration-response-effects of physostigmine and neostigmine on the oxidative burst activity (human and rat PMN) and the expression of adhesion molecules on the surface of human PMN under in vitro conditions.MethodsPMN from 10 healthy humans or 10 rats were pretreated with 2, 10, 24, 97 μM physostigmine or 3, 15, 30, 150 μM neostigmine, primed with tumor-necrosis-factor-alpha (TNF-alpha) followed by stimulation with n-formyl-methionyl-leucylphenylalanine (fMLP) or stimulated with phorbol-12-myristate-13-acetate (PMA). Human and rat samples were assessed by flow cytometry for the generation of oxidative free radicals. Stimulated human PMN were additionally incubated with antibodies against Mac-1 (CD11b) or L-selectin (CD62l).ResultsPhysostigmine and neostigmine did not alter oxidative burst activity or the expression of adhesion molecules of PMN induced by receptor-dependent activators like fMLP or TNF-alpha/fMLP (rat and human PMN, p=n.s.). Physostigmine, but not neostigmine, inhibited the protein-kinase-C-mediated oxidative burst activity by PMA in a dose-dependent manner (rat and human PMN, p<0.05). Physostigmine, in the concentration range tested, suppressed the expression of CD11b following stimulation with PMA not significantly (human PMN: control: 63.1±10.7 vs. 97 μM physostigmine: 49.9±12.8 MESF, p=n.s.).ConclusionWhile neostigmine has no effect on functional and phenotypic changes of PMN, the lipid soluble Ch-I physostigmine causes a dose dependent reduction in PMA-induced oxidative burst, independent of neuronal released acetylcholine.Copyright © 2013 Elsevier GmbH. All rights reserved.

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