Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.
Abstract: Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction. Methods: We measured the response of six heaves horses following inhalation of saline (placebo) and three doses of Aspergillus fumigatus extract. We then compared the response of six heaves horses to A. fumigatus extract inhalation before and after lipopolysaccharide (LPS) depletion. Results: Inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract resulted in a significant increase in bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation. Only 1.6 and 5 mg extract inhalation resulted in significant lung dysfunction compared with saline. There was no significant difference between 1.6 and 5 mg extract inhalation with respect to airway neutrophil numbers or lung function, suggesting a plateau in both measured responses. LPS depletion of 1.6 mg A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers and increase in arterial oxygen tension. There was no significant difference between saline and the LPS-depleted A. fumigatus extract challenges with respect to neutrophil count and lung function. The reduction in airway neutrophil numbers was greater than would be predicted by extrapolation from previously reported soluble LPS dose-response inhalation experiments. Conclusions: This study supports a role for other inhalants, in addition to soluble components of A. fumigatus, in the aetiopathogenesis of heaves. Also the amplification in response to LPS when inhaled with A. fumigatus extract, suggests that the role of inhaled endotoxin in the pulmonary inflammation and dysfunction in naturally occurring heaves may currently be underestimated.
Publication Date: 2003-09-06 PubMed ID: 12956737DOI: 10.1046/j.1365-2745.2003.01651.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses a study conducted on heaves horses to examine the influence of Aspergillus fumigatus extract inhalation, particularly the role of endotoxin contamination, on pulmonary inflammation and dysfunction. The study results show that inhaled endotoxin may play a significant role in lung inflammation and malfunction in heaves, which was previously underestimated.
Methods of Research
- The researchers utilized a group of six heaves horses for this study.
- The horses were subjected to inhalation of saline (used as a placebo) and three different doses of Aspergillus fumigatus extract.
- The reactions of the horses to the extract inhalation were monitored before and after lipopolysaccharide (LPS) depletion – a process used to minimize endotoxin contamination.
Findings of the Research
- It was discovered that inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract significantly increased bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation.
- However, only inhalation of 1.6 and 5 mg extract resulted in significant lung dysfunction.
- There were no significant differences between 1.6 and 5 mg extract inhalation regarding airway neutrophil numbers or lung function, indicating a plateau in responses.
- Interestingly, LPS depletion of 1.6 mg A. fumigatus extract led to a significant decrease in airway neutrophil numbers and increase in arterial oxygen tension.
- When compared to saline and the LPS-depleted A. fumigatus extract challenges, no significant differences were noted regarding neutrophil count and lung function.
Conclusions of the Research
- The study supports the premise that inhaled endotoxin, along with the soluble components of A. fumigatus, plays a crucial role in the development and progression of heaves.
- The study also suggests that inhaled endotoxin’s part in lung inflammation and malfunction in naturally occurring heaves may be currently underrated.
Implications of the Research
- The findings point towards the significance of considering endotoxin contamination when studying lung inflammation and dysfunction in horses.
- This elucidation can provide input for developing successful therapeutic strategies targeting pulmonary conditions in horses, especially heaves.
Cite This Article
APA
Pirie RS, Dixon PM, McGorum BC.
(2003).
Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.
Clin Exp Allergy, 33(9), 1289-1296.
https://doi.org/10.1046/j.1365-2745.2003.01651.x Publication
Researcher Affiliations
- Department of Veterinary Clinical Studies, Easter Bush Veterinary Centre, Roslin, UK. scottp@staffmail.ed.ac.uk
MeSH Terms
- Animal Feed
- Animals
- Aspergillus fumigatus / immunology
- Bronchoalveolar Lavage Fluid / immunology
- Dose-Response Relationship, Drug
- Dust
- Endotoxins / analysis
- Endotoxins / immunology
- Female
- Horse Diseases / immunology
- Horses
- Inflammation / immunology
- Lipopolysaccharides / immunology
- Lung Diseases / immunology
- Lung Diseases / veterinary
- Male
- Neutrophils / immunology
- Plant Extracts / immunology
Citations
This article has been cited 10 times.- Basano I, Romolo A, Iamone G, Memoli G, Riccio B, Lavoie JP, Miniscalco B, Bullone M. Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma.. Animals (Basel) 2022 Apr 20;12(9).
- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
- White S, Moore-Colyer M, Marti E, Coüetil L, Hannant D, Richard EA, Alcocer M. Development of a comprehensive protein microarray for immunoglobulin E profiling in horses with severe asthma.. J Vet Intern Med 2019 Sep;33(5):2327-2335.
- Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.. BMC Genomics 2017 Jan 5;18(1):34.
- Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
- Sandersen C, Bienzle D, Cerri S, Franck T, Derochette S, Neven P, Mouytis-Mickalad A, Serteyn D. Effect of inhaled hydrosoluble curcumin on inflammatory markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neutrophilia.. Multidiscip Respir Med 2015;10(1):16.
- Wan GH, Yan DC, Tung TH, Tang CS, Liu CH. Seasonal Changes in Endotoxin Exposure and Its Relationship to Exhaled Nitric Oxide and Exhaled Breath Condensate pH Levels in Atopic and Healthy Children.. PLoS One 2013;8(6):e66785.
- Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction.. BMC Vet Res 2012 May 23;8:64.
- Kulhankova K, George CL, Kline JN, Snyder JM, Darling M, Field EH, Thorne PS. Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responses.. Clin Exp Allergy 2009 Jul;39(7):1069-79.
- Riihimäki M, Raine A, Elfman L, Pringle J. Markers of respiratory inflammation in horses in relation to seasonal changes in air quality in a conventional racing stable.. Can J Vet Res 2008 Oct;72(5):432-9.
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