Modulation of eosinophil activation in vitro by a nicotinic receptor agonist

Blanchet, Marie‐Renée; Langlois, Anick; Israël-Assayag, Évelyne; Beaulieu, Marie‐Josée; Ferland, Claudine; Laviolette, Michel; Cormier, Yvon

doi:10.1189/jlb.0906548

Cited by 41 publications

(42 citation statements)

References 36 publications

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“…Platelet RNA was obtained from 5ϫ10 8 leukocytedepleted platelets as described in detail previously. 28 cDNA was generated using the Transcriptor First Strand cDNA Synthesis Kit (Roche Applied Science, Mannheim, Germany).…”

Section: Real-time Polymerase Chain Reaction For Mrna Detection and Rmentioning

confidence: 99%

Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

Schedel

Thornton

Schloss

et al. 2011

ATVB

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Objective-Nicotinic acetylcholine receptors, especially ␣7 (nAChR␣7), form Ca 2ϩ channels and are expressed on a variety of neuronal and nonneuronal cells. Also, megakaryocytic cells have been shown to contain components of a nonneuronal cholinergic system, including acetylcholine and acetylcholine esterase. However, the corresponding nAChRs and their role in platelet function have not been demonstrated until now. Our previous platelet transcriptome data indicated the presence of nAChR gene transcripts. Methods and Results-Here, we present evidence that human platelets and megakaryocytic precursor cells express nAChR␣7 subunits, as revealed by mRNA and protein expression. The subunits form functional Ca 2ϩ channels, as demonstrated by Ca 2ϩ entry in platelets induced by the nAChR␣7-selective agonist PNU-282987. PNU-282987 also enhanced fibrinogen receptor activation induced by classical platelet agonists (the thromboxane A 2 analog U46619 and ADP). Furthermore, agonist-induced platelet aggregation was significantly inhibited by the nAChR␣7-selective antagonists ␣-bungarotoxin and methyllycaconitine. Conclusion-Ca2ϩ influx via nAChR␣7 channels represents a novel pathway for human platelets with significant impact on platelet function. Because platelets were suggested to contain acetylcholine, we conclude that on activation, stored acetylcholine is released, which activates nAChR␣7 channels and thereby contributes to maintaining intracellular Ca

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Section: Real-time Polymerase Chain Reaction For Mrna Detection and Rmentioning

confidence: 99%

Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

Schedel

Thornton

Schloss

et al. 2011

ATVB

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“…It demonstrated both anti-inflammatory and smooth muscle relaxant properties (20)(21)(22). ASM-024, a quaternary ammonium compound and an analogue of DMPP, has anti-inflammatory, smooth muscle relaxant and bronchoprotective properties in various in vitro and in vivo models (23).…”

Section: Discussionmentioning

confidence: 99%

Effects of Asm‐024, A Modulator of Acetylcholine Receptor Function, On Airway Responsiveness and Allergen‐Induced Responses in Patients with Mild Asthma

Boulet

Gauvreau²,

Cockcroft³

et al. 2015

Canadian Respiratory Journal

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OBJECTIVES: To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma.METHODS: The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured.RESULTS: Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo −1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo.CONCLUSIONS: ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.

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“…Monocytes have nicotinic ACh receptors that are involved in the synthesis of C2, the second component of complement [52]. Eosinophils have anti-inflammatory alpha-3, -4 and -7 nicotinic ACh receptors that down regulate eosinophil activity [53].…”

Section: Acetylcholine (Nicotinic)mentioning

confidence: 99%

Some Aspects of the Normal Role of Neuromodulators in the Immune System

Smythies¹

2011

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Modulation of eosinophil activation in vitro by a nicotinic receptor agonist

Cited by 41 publications

References 36 publications

Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

Effects of Asm‐024, A Modulator of Acetylcholine Receptor Function, On Airway Responsiveness and Allergen‐Induced Responses in Patients with Mild Asthma

Some Aspects of the Normal Role of Neuromodulators in the Immune System

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