Allergen and Ozone Exacerbate Serotonin-induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

Overview

Journal Respiration

Publisher Karger

Specialty Pulmonary Medicine

Date 2012 Apr 18

PMID 22507883

Citations 18

Authors

Brian D Moore

Dallas Hyde

Lisa Miller

Emily Wong

Jessica Frelinger

Edward S Schelegle

Affiliations

Soon will be listed here.

Abstract

Background: Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O(3)) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity.

Objectives: In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O(3) and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction.

Methods: Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O(3) or in combination (HDMA+O(3)). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS).

Results: 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT(2), 5-HT(3) and 5-HT(4) receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT(2), 5-HT(3) and 5-HT(4) receptors. Conversely, a 5-HT(1) receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine.

Conclusions: HDMA, O(3) and HDMA+O(3) exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT(2), 5-HT(3) and 5-HT(4) receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT(1) receptors located on ASM.

Citing Articles

"Air That Once Was Breath" Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation - "Climate Change, Allergy and Immunology" Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023.

Bowman W, Schmidt R, Sanghar G, Thompson Iii G, Ji H, Zeki A Int Arch Allergy Immunol. 2024; 185(6):600-616.

PMID: 38452750 PMC: 11487202. DOI: 10.1159/000536578.

Expression of airway smooth muscle contractile proteins in children with acute interstitial pneumonia.

Cheng F, Lu T, Wang Y, Yuan D, Wei Z, Li Y Int J Exp Pathol. 2022; 103(5):190-197.

PMID: 35527237 PMC: 9482355. DOI: 10.1111/iep.12443.

Air pollution and hospitalization of patients with idiopathic pulmonary fibrosis in Beijing: a time-series study.

Liang L, Cai Y, Lyu B, Zhang D, Chu S, Jing H Respir Res. 2022; 23(1):81.

PMID: 35382829 PMC: 8985349. DOI: 10.1186/s12931-022-01998-8.

Ozone-Induced Oxidative Stress, Neutrophilic Airway Inflammation, and Glucocorticoid Resistance in Asthma.

Enweasor C, Flayer C, Haczku A Front Immunol. 2021; 12:631092.

PMID: 33717165 PMC: 7952990. DOI: 10.3389/fimmu.2021.631092.

Exposure to ozone impacted Th1/Th2 imbalance of CD T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

Wei Y, Han B, Dai W, Guo S, Zhang C, Zhao L Aging (Albany NY). 2020; 12(24):25229-25255.

PMID: 33223504 PMC: 7803560. DOI: 10.18632/aging.104124.

References

Schelegle E, Adams W . Reduced exercise time in competitive simulations consequent to low level ozone exposure. Med Sci Sports Exerc. 1986; 18(4):408-14. View

Ju J, Hwang J, Piao L, Park H, Park J, Shin D . Ketanserin, a 5-HT2 antagonist, directly inhibits the ATP-sensitive potassium channel in mouse ventricular myocytes. J Cardiovasc Pharmacol. 2006; 47(1):96-102. DOI: 10.1097/01.fjc.0000196238.51018.e9. View

Soulier J, Russo O, Giner M, Rivail L, Berthouze M, Ongeri S . Design and synthesis of specific probes for human 5-HT4 receptor dimerization studies. J Med Chem. 2005; 48(20):6220-8. DOI: 10.1021/jm050234z. View

Rizzo C, Kreutner W, Chapman R . 5-HT3 receptors augment neuronal, cholinergic contractions in guinea pig trachea. Eur J Pharmacol. 1993; 234(1):109-12. DOI: 10.1016/0014-2999(93)90712-q. View

McConnell R, Berhane K, Gilliland F, London S, Islam T, Gauderman W . Asthma in exercising children exposed to ozone: a cohort study. Lancet. 2002; 359(9304):386-91. DOI: 10.1016/S0140-6736(02)07597-9. View

Lechin F, van der Dijs B, Lechin A . Tianeptine: a new exploratory therapy for asthma. Chest. 2004; 125(1):348-9. DOI: 10.1378/chest.125.1.348. View

Plopper C, Weir A, Nishio S, Cranz D, St George J . Tracheal submucosal gland development in the rhesus monkey, Macaca mulatta: ultrastructure and histochemistry. Anat Embryol (Berl). 1986; 174(2):167-78. DOI: 10.1007/BF00824332. View

. Dust mite allergens and asthma--a worldwide problem. J Allergy Clin Immunol. 1989; 83(2 Pt 1):416-27. DOI: 10.1016/0091-6749(89)90128-0. View

Youssefyeh R, Campbell H, Klein S, Airey J, Darkes P, Powers M . Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides. J Med Chem. 1992; 35(5):895-903. DOI: 10.1021/jm00083a014. View

10.

Tuladhar B, Costall B, Naylor R . Modulation of 5-HT4 receptor function in the rat isolated ileum by fluoxetine: the involvement of endogenous 5-hydroxytryptamine. Br J Pharmacol. 2002; 136(1):150-6. PMC: 1762121. DOI: 10.1038/sj.bjp.0704694. View

11.

Pindon A, van Hecke G, van Gompel P, Lesage A, Leysen J, Jurzak M . Differences in signal transduction of two 5-HT4 receptor splice variants: compound specificity and dual coupling with Galphas- and Galphai/o-proteins. Mol Pharmacol. 2001; 61(1):85-96. DOI: 10.1124/mol.61.1.85. View

12.

Koren H . Associations between criteria air pollutants and asthma. Environ Health Perspect. 1995; 103 Suppl 6:235-42. PMC: 1518942. DOI: 10.1289/ehp.95103s6235. View

13.

Dupont L, Pype J, Demedts M, De Leyn P, Deneffe G, Verleden G . The effects of 5-HT on cholinergic contraction in human airways in vitro. Eur Respir J. 1999; 14(3):642-9. DOI: 10.1034/j.1399-3003.1999.14c26.x. View

14.

Evans M, Fanucchi M, BAKER G, Van Winkle L, Pantle L, Nishio S . The remodelled tracheal basement membrane zone of infant rhesus monkeys after 6 months of recovery. Clin Exp Allergy. 2004; 34(7):1131-6. DOI: 10.1111/j.1365-2222.2004.02004.x. View

15.

Bertelsen R, Lodrup Carlsen K, Carlsen K, Granum B, Doekes G, Haland G . Childhood asthma and early life exposure to indoor allergens, endotoxin and beta(1,3)-glucans. Clin Exp Allergy. 2010; 40(2):307-16. DOI: 10.1111/j.1365-2222.2009.03424.x. View

16.

Kajekar R, Pieczarka E, Smiley-Jewell S, Schelegle E, Fanucchi M, Plopper C . Early postnatal exposure to allergen and ozone leads to hyperinnervation of the pulmonary epithelium. Respir Physiol Neurobiol. 2006; 155(1):55-63. DOI: 10.1016/j.resp.2006.03.002. View

17.

Joad J, Kott K, Bric J, Peake J, Plopper C, Schelegle E . Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone. Toxicol Appl Pharmacol. 2006; 214(3):237-43. DOI: 10.1016/j.taap.2005.12.012. View

18.

Glennon R, Lee M, Rangisetty J, Dukat M, Roth B, SAVAGE J . 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000; 43(5):1011-8. DOI: 10.1021/jm990550b. View

19.

Gale J, Grossman C, Whitehead J, Oxford A, Bunce K, Humphrey P . GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. Br J Pharmacol. 1994; 111(1):332-8. PMC: 1910004. DOI: 10.1111/j.1476-5381.1994.tb14064.x. View

20.

Lechin F, van der Dijs B, Lechin A . Treatment of bronchial asthma with tianeptine. Methods Find Exp Clin Pharmacol. 2005; 26(9):697-701. DOI: 10.1358/mf.2004.26.9.872567. View