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

Bitzinger, Diane; Zausig, York; Paech, Christoph; Gruber, Michael; Busse, Hendrik; Sinner, Barbara; Graf, Bernhard M.; Trabold, Benedikt

doi:10.1016/j.imbio.2013.01.003

Cited by 9 publications

(11 citation statements)

References 21 publications

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“…One difference between neostigmine and physostigmine is the site of action. We compared treatment with physostigmine, which is lipid-soluble and crosses the blood-brain barrier, to treatment with neostigmine, which only acts in the periphery [12, 25].…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats

Bitzinger

Gruber

Tümmler

et al. 2019

Mediators of Inflammation

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Introduction Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. Methods Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 μg/kg; neostigmine, 75 μg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. Results CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. Conclusion While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.

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Section: Discussionmentioning

confidence: 99%

“…(1) Oxidative Burst Assay . The oxidative burst assay has been performed as described previously [24, 25]. For quantifying the oxidative burst, 2 × 10 μ L heparinized whole blood was collected at the five time points indicated in Figure 1.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats

Bitzinger

Gruber

Tümmler

et al. 2019

Mediators of Inflammation

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“…The methods used were: an oxidative burst to observe ROS production, and detection of cell-surface antigens CD11b, CD62L and CD66b. 21,22 For the oxidative burst, cells were preincubated in 1 mL of Dulbecco's phosphate-buffered saline (DPBS, Sigma Aldrich, Steinheim, Germany), 10 µL DHR 123 (10 µM), and 10 µL seminaphtharhodafluor (SNARF, 10 µM, Invitrogen, Eugene, USA). The oxidative burst was triggered by adding either 10 µL fMLP (10 µM) and 10 µL tumor necrosis factor alpha (TNFa, 1 µg/mL, Pepro Tech Inc., Rocky Hill, USA), or 10 µL phorbol-12-myristate-13-acetate (PMA; 10 µM, Sigma-Aldrich).…”

Section: Flow Cytometrymentioning

confidence: 99%

Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome

Kolle¹,

Metterlein²,

Gruber³

et al. 2021

JIR

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“…Physostigmine can be used for alleviation of glaucoma manifestation [102] and it is suitable for the treatment of Alzheimer disease [103,104]. As discussed later in the text, physostigmine can inhibit protein kinase C. This ability is not common to other carbamate inhibitors of cholinesterases [105]. Physostigmine was shown to increase the availability of ACh and stimulate the cholinergic anti-inflammatory pathway in experimental endotoxemia by lipopolysaccharide [106].…”

Section: Inhibitors That Cross the Blood Brain Barriermentioning

confidence: 99%

“…Regulation of immunity can be based on pathways far from the cholinergic system. e.g., Bitzinger et al revealed the ability of physostigmine to inhibit protein kinase C while neostigmine did not have this ability [105]. …”

Section: Peripherally Acting Carbamates-parasympathomimeticsmentioning

confidence: 99%

Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

Pohanka

2014

IJMS

204

112

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Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.

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

Cited by 9 publications

References 21 publications

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats

Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome

Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

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