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Pulmonary pharmacology & therapeutics2018; 49; 88-94; doi: 10.1016/j.pupt.2018.01.010

Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue.

Abstract: Recurrent airway obstruction (RAO) is a main characteristic of horses with severe equine asthma syndrome. The presence of bacterial lipopolysaccharide (LPS) in the airways of horses is thought to play a crucial role in the clinical expression of this disorder. This study pharmacologically characterized the effect of LPS on the responsiveness of equine bronchial tissue. Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml) and then stimulated by electrical field stimulation (EFS). The role of capsaicin sensitive-sensory nerves (capsaicin desensitization treatment), neurokinin-2 (NK) receptors (blocked by GR159897), transient receptor potential vanilloid type 1 receptors (TRPV1; blocked by SB366791), and neurokinin A (NKA) were investigated. Untreated bronchi were used as control tissues. LPS (1 ng/ml) significantly increased the EFS-evoked contractility of equine bronchi compared with control tissues (+742 ± 123 mg; P < 0.001). At higher concentrations LPS induced desensitization to airways hyperresponsiveness (AHR; EC: 5.9 ± 2.6 ng/ml). Capsaicin desensitization and GR159897 significantly prevented AHR induced by LPS at EFS (-197 ± 25%; P < 0.01). SB366791 inhibited AHR at very low EFS frequency (EFS -193 ± 29%; P < 0.01 vs. LPS-treated bronchi). LPS (1 ng/ml) significantly (P < 0.01) increased 3.7 ± 0.7 fold the release of NKA compared with control bronchi. LPS induces biphasic dysfunctional bronchial contractility due to the stimulation of capsaicin sensitive-sensory nerves, increased release of NKA, and activation of NK receptors, whereas TRPV1 receptors appear to play a marginal role in this response. The overnight challenge with low concentrations of LPS represents a suitable model to investigate pharmacological options that may be of value in the treatment of equine RAO.
Publication Date: 2018-01-31 PubMed ID: 29408044DOI: 10.1016/j.pupt.2018.01.010Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores how the bacterial substance lipopolysaccharide (LPS) affects horse bronchial tissue response, and its potential role in equine asthma syndrome. Experimentation includes stimulation and various treatments on dissected bronchi, revealing that LPS may lead to dysfunctional bronchial contractility and boost related receptor activity.

Study Design and Methods

  • The researchers focused on recurrent airway obstruction (RAO), a primary trait of severe equine asthma syndrome, hypothesizing that LPS present in horse airways could be an influential factor.
  • Horse bronchi samples were isolated and exposed to varying amounts of LPS (0.1-100 ng/ml) overnight, then stimulated using electrical field stimulation (EFS). The control group comprised untreated bronchi samples.
  • The contributions of capsaicin sensitive-sensory nerves, neurokinin-2 (NK) receptors, transient receptor potential vanilloid type 1 receptors (TRPV1), and neurokinin A (NKA) were inspected using capsaicin desensitization treatment, GR159897, SB366791, and the release of NKA respectively.

Results

  • Findings showed a considerable rise in the EFS-evoked contractility of horse bronchi with an LPS concentration of 1 ng/ml compared to the control group. This indicated an increased reactivity of bronchi tissues to LPS.
  • At higher LPS concentrations, a desensitisation effect was observed, which reduced airways hyperresponsiveness.
  • Capsaicin desensitization and NK receptor blocking (by GR159897) significantly reduced the increased airway response induced by LPS.
  • The use of SB366791 substantially inhibited elevated bronchi response at very low EFS frequency.
  • A noteworthy increase in the release of NKA was observed with an LPS concentration of 1 ng/ml.

Conclusion and Implications

  • These results suggest that LPS can lead to impaired bronchial contractility by stimulating capsaicin sensitive-sensory nerves, activating NK receptors, and increasing release of NKA.
  • TRPV1 receptors appear to play a minor role.
  • The study also suggests that experimentation with low concentrations of LPS may be appropriate for further research toward potential therapeutic methods for equine RAO.

Cite This Article

APA
Calzetta L, Rogliani P, Pistocchini E, Mattei M, Cito G, Alfonsi P, Page C, Matera MG. (2018). Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue. Pulm Pharmacol Ther, 49, 88-94. https://doi.org/10.1016/j.pupt.2018.01.010

Publication

ISSN: 1522-9629
NlmUniqueID: 9715279
Country: England
Language: English
Volume: 49
Pages: 88-94
PII: S1094-5539(18)30004-X

Researcher Affiliations

Calzetta, Luigino
  • Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. Electronic address: luigino.calzetta@uniroma2.it.
Rogliani, Paola
  • Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
Pistocchini, Elena
  • CDVet, Laboratorio Analisi Veterinarie, Rome, Italy.
Mattei, Maurizio
  • Department of Biology, Centro Servizi Interdipartimentale-STA, University of Rome Tor Vergata, Rome, Italy.
Cito, Giuseppe
  • ASL Roma 2, UOC Tutela Igienico Sanitaria Degli Alimenti di Origine Animale, Rome, Italy.
Alfonsi, Pietro
  • ASL Roma 2, UOC Igiene Degli Allevamenti e Delle Produzioni Zootecniche, Rome, Italy.
Page, Clive
  • The Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
Matera, Maria Gabriella
  • Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.

MeSH Terms

  • Airway Obstruction / physiopathology
  • Airway Obstruction / veterinary
  • Anilides / pharmacology
  • Animals
  • Asthma / physiopathology
  • Asthma / veterinary
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Capsaicin / administration & dosage
  • Cinnamates / pharmacology
  • Disease Models, Animal
  • Electric Stimulation
  • Female
  • Horse Diseases / physiopathology
  • Horses
  • Lipopolysaccharides / administration & dosage
  • Male
  • Neurokinin A / metabolism
  • Respiratory Hypersensitivity / physiopathology
  • Respiratory Hypersensitivity / veterinary

Citations

This article has been cited 2 times.
  1. Morini M, Peli A, Rinnovati R, Magazzù G, Romagnoli N, Spadari A, Pietra M. Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase. Animals (Basel) 2021 May 12;11(5).
    doi: 10.3390/ani11051376pubmed: 34066204google scholar: lookup
  2. Braucke AFGV, Frederiksen NL, Berg LC, Aarsvold S, Müller FC, Boesen MP, Lindegaard C. Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue. Animals (Basel) 2020 Mar 18;10(3).
    doi: 10.3390/ani10030506pubmed: 32197454google scholar: lookup