Mediators of anaphylaxis but not activated neutrophils augment cholinergic responses of equine small airways.
Abstract: Neutrophilic inflammation in small airways (SA) and bronchospasm mediated via muscarinic receptors are features of chronic obstructive pulmonary disease in horses (COPD). Histamine, serotonin, and leukotrienes (LTs) are reported to be involved in the exacerbation of COPD, and currently, histamine has been shown to increase tension response to electrical field simulation (EFS) in equine SA. We tested the effects of these mediators and the effects of activated neutrophils on the cholinergic responses in SA. Histamine, serotonin, and LTD4 had a synergistic effect on EFS responses and only an additive effect on the tension response to exogenous ACh or methacholine. Atropine and TTX entirely eliminated the EFS-induced tension response in the presence of all three inflammatory mediators, indicating that augmentation of the EFS response applies only to the endogenous cholinergic response. Neutrophils isolated from control and COPD-affected horses were activated by zymosan, producing 18.1 +/- 2.3 and 25.0 +/- 2.3 nmol superoxide. 10(6) cells-1. 30 min-1, respectively. However, in contrast to the profound effect of mediators, incubation of SA for over 1 h in a suspension of up to 30 x 10(6) zymosan-treated neutrophils/ml did not significantly affect EFS responses of SA isolated from either control or COPD-affected horses. We conclude that in equine SA 1) the endogenous cholinergic responses are subject to strong facilitation by inflammatory mediators; 2) activated neutrophils do not affect cholinergic responses in SA; and 3) in acute bouts of equine COPD, histamine, LTD4, and serotonin (mediators primarily associated with type I allergic reaction) rather than mediators derived from neutrophils most likely contribute to increased cholinergic airway tone.
Publication Date: 1999-03-10 PubMed ID: 10070118DOI: 10.1152/ajplung.1999.276.3.L522Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Atropine
- Chronic Obstructive Pulmonary Disease
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Health
- Histamine
- Horses
- Immune Response
- In Vivo
- Inflammation
- Inflammatory Response
- Musculoskeletal System
- Neutrophils
- Pathophysiology
- Pharmacology
- Physiology
- Pulmonary Health
- Respiratory Disease
- Serotonin
- Veterinary Medicine
Summary
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The research studies the effects of different inflammatory mediators and activated neutrophils on small airways in horses suffering from chronic obstructive pulmonary disease (COPD). The findings reveal that though inflammatory mediators significantly facilitate the endogenous cholinergic response, activated neutrophils do not influence this response. The study also concludes that in acute COPD outbreaks in horses, specific mediators such as histamine, LTD4, and serotonin are more likely responsible for increased cholinergic airway tone.
Thorough Explanation of the Research
- This research focused on uncovering the impact of different inflammatory mediators like histamine, serotonin, and leukotrienes (LTs), and activated neutrophils on equine small airways (SA) affected by chronic obstructive pulmonary disease (COPD). COPD in horses exhibits features like neutrophilic inflammation and bronchospasm, which is controlled through muscarinic receptors.
- Earlier studies have shown that histamine augments the tension response to electrical field stimulation (EFS) in equine SA. The authors of this research examined the combined effect of the mentioned mediators and the impact of activated neutrophils on the cholinergic response in the SA.
- The researchers discovered that histamine, serotonin, and LTD4, when acting together, increased responses to the EFS and had a cumulative effect on the tension response to exogenous Acetylcholine (ACh) or methacholine. EFS-induced tension response was entirely eradicated in the presence of these three inflammatory mediators by Atropine and TTX, signaling that this augmenting effect applies only to the endogenous cholinergic response.
- For investigating the effect of neutrophils, they were isolated from both control and COPD-affected horses. These cells were activated by zymosan, generating significant superoxide. Despite the potent effect of the inflammatory mediators, the addition of up to 30 x 10(6) zymosan-treated neutrophils/ml to a suspension of SA didn’t cause significant changes to the EFS responses of the SA from either control or COPD-affected horses, contrary to expectation.
- In conclusion, the study demonstrates that in equine SAs, the endogenous cholinergic responses are strongly affected by inflammatory mediators but remain unaffected by activated neutrophils. In acute bouts of equine COPD, inflammatory mediators (histamine, LTD4, and serotonin) significantly linked with type I allergic reaction seem to contribute more to the increased cholinergic airway tone than mediators derived from neutrophils.
Cite This Article
APA
Olszewski MA, Robinson NE, Zhu FX, Zhang XY, Tithof PK.
(1999).
Mediators of anaphylaxis but not activated neutrophils augment cholinergic responses of equine small airways.
Am J Physiol, 276(3), L522-L529.
https://doi.org/10.1152/ajplung.1999.276.3.L522 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan 48824, USA.
MeSH Terms
- Anaphylaxis / etiology
- Animals
- Cholinergic Fibers / physiology
- Female
- Histamine / pharmacology
- Horse Diseases / physiopathology
- Horses / physiology
- Inflammation Mediators / physiology
- Leukotriene D4 / pharmacology
- Lung Diseases, Obstructive / veterinary
- Male
- Neutrophil Activation / physiology
- Neutrophils / physiology
- Respiratory System / innervation
- Serotonin / pharmacology
Citations
This article has been cited 3 times.- Lo Feudo CM, Stucchi L, Alberti E, Conturba B, Zucca E, Ferrucci F. Intradermal Testing Results in Horses Affected by Mild-Moderate and Severe Equine Asthma.. Animals (Basel) 2021 Jul 13;11(7).
- Khol-Parisini A, van den Hoven R, Leinker S, Hulan HW, Zentek J. Effects of feeding sunflower oil or seal blubber oil to horses with recurrent airway obstruction.. Can J Vet Res 2007 Jan;71(1):59-65.
- Art T, Franck T, Lekeux P, de Moffarts B, Couëtil L, Becker M, Kohnen S, Deby-Dupont G, Serteyn D. Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction.. Can J Vet Res 2006 Oct;70(4):291-6.
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