Mechanisms of allergy and clinical immunologyRole of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo
Section snippets
Methods
NHBE and A549 cells were cultured by using standard procedures.15 DO11.10 ovalbumin (OVA)–T-cell receptor (TCR) transgenic mice on a BALB/c background were exposed to air, secondhand smoke (SS) or nicotine (1.5 mg total particulate material/m3), heat-aggregated OVA aerosol (5 mg/m3), or OVA plus SS or nicotine for 2 weeks (6 h/d for 5 d/wk). In some experiments normal (wild-type) BALB/c mice were sensitized to Aspergillus fumigatus extract, as described previously.16 Where indicated, mice were
Nicotinic receptors are critical in mucus formation
We examined the effects of nicotine (100 nmol/L) on mucus formation in NHBE cells grown at the air-liquid interface (ALI). This is a realistic concentration of nicotine and is several-fold lower than the median effective concentration (10-100 μmol/L) of nicotine/nicotine agonists required to activate the ligand-gated cationic channel in neurons.22 As seen with AB/PAS mucus staining (Fig 1, A), control NHBE cells have a low baseline level of mucus; however, when the cells were treated with
Discussion
NAChRs are seen in tissues from both vertebrates and invertebrates, such as nematodes and insects.40 In the central nervous system nAChRs are ligand-gated ion channels that mediate fast synaptic cholinergic transmission, and these properties are strongly conserved across species. nAChRs are present in neuronal32 and many nonneuronal13, 29, 30 cell types. At least in some nonneuronal cell types nAChRs are not ligand-gated ion channels but signal through second messengers.29 Thus far, the
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Nicotinic acetylcholine receptor subtype expression, function, and pharmacology: Therapeutic potential of α-conotoxins
2023, Pharmacological ResearchResidual Risk of Nicotine
2021, Toxicological Evaluation of Electronic Nicotine Delivery ProductsVesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles
2019, Ecotoxicology and Environmental SafetyPossible involvement of acetylcholine-mediated inflammation in airway diseases
2018, Allergology InternationalCitation Excerpt :Nicotinic receptors are ligand-gated ion channels and are localized to parasympathetic ganglia, where they facilitate neurotransmission5,16 (Fig. 1). Nicotinic receptors are also present in various cells including airway epithelial cells, macrophages, lymphocytes and type 2 innate lymphoid cells,16–21 and the stimulation of nicotinic receptors mainly causes putative anti-inflammatory effects, but also causes mucus formation in airway epithelial cells and a proliferative effect on tumors.16,22 Currently available LAMAs show similar affinity to M1, M2, and M3.
Tiotropium inhibits mucin production stimulated by neutrophil elastase but not by IL-13
2018, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :However, while tiotropium did decrease MUC5AC stimulated by NE, it had no effect on IL-13 induced mucin secretion or goblet cell metaplasia. Non-neuronal acetylcholine secreted by airway epithelium cells binds to M3R and induces inflammation and mucin production [6,7,20], and increased M3R expression appears to enhance these responses. It is reported that a murine knock-out of M3R, but not M1R or M2R, prevented both the inflammatory response induced by cigarette smoke and allergen-induced goblet cell metaplasia [6,21].
Supported in part by grants from the US Army Medical Research and Material Command (GW093005), the National Institutes of Health (R01-DA017003), and the Lovelace Respiratory Research Institute (IMMSPT).
Disclosure of potential conflict of interest: K. S. Harrod is a member of the Avisa Pharma Board of Directors. The rest of the authors declare that they have no relevant conflicts of interest.