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Equine Asthma Is Characterised by Severity-Dependent Correlations Between Blood Neutrophil Cholesterol Content and NET Formation.
Abstract: Equine asthma (EA) is the most prevalent chronic lung disease in horses. Neutrophils are the main effector cells in severe EA. Neutrophil extracellular traps (NETs) have been described as contributors to severity in human asthma and chronic obstructive pulmonary disease. Thus, we aimed to investigate if NET-related factors in equine neutrophils, blood and bronchoalveolar lavage fluid (BALF) allow us to differentiate EA severities and to identify NET-related mechanistic insights in EA. We quantified NETs and NET-related factors in the blood and BALF of eight healthy horses and 18 horses with differing EA severities. The proportion of activated cells in BALF increased with EA severity, accompanied by dysregulation of local NET regulators in severe EA. Furthermore, circulating anti-neutrophil cytoplasmic antibodies (ANCAs = NET-autoantibodies) were found elevated in severely diseased horses. In line with these findings, NET formation by circulating neutrophils was found to depend on the severity of EA. Finally, we analysed the cholesterol content of circulating neutrophils and identified an asthma-severity-dependent decrease in cellular cholesterol, which correlated with increased NET formation and hypoxia. Local and systemic modifications-particularly in neutrophil cellular cholesterol content-provide further insight into the partially understood pathogenesis of EA and point to a systemic cholesterol-associated inflammatory component fuelling disease progression.
© 2025 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.
Publication Date: 2025-10-07 PubMed ID: 41054022PubMed Central: PMC12501399DOI: 10.1002/eji.70072Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Animal Study
- Asthma
- Biomarkers
- Blood
- Bronchoalveolar Lavage
- Cholesterol
- Chronic Obstructive Pulmonary Disease
- Clinical Study
- Disease Management
- Disease Severity
- Equine Diseases
- Immune Response
- Immunology
- Inflammation
- Laboratory Methods
- Neutrophils
- Pathogenesis
- Respiratory Disease
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
Equine asthma (EA) severity correlates with changes in neutrophil behavior, including the formation of neutrophil extracellular traps (NETs) and alterations in neutrophil cholesterol content, which may contribute to disease progression and inflammation.
Background and Purpose
- Equine asthma (EA) is the most common chronic lung disease in horses, with varying severities.
- Neutrophils, a type of white blood cell, play a central role in the severe forms of EA.
- Neutrophil extracellular traps (NETs) are web-like structures released by neutrophils that contribute to inflammation and tissue damage in human respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
- The study aims to investigate how NET formation and related factors in equine neutrophils, blood, and lung fluid (bronchoalveolar lavage fluid, BALF) differ according to EA severity.
- The researchers also sought to explore the possible mechanisms linking NETs and disease progression in EA.
Methods
- Subjects included eight healthy horses and eighteen horses diagnosed with varying severities of EA.
- NETs and NET-related factors were quantified both in systemic circulation (blood) and locally in the lungs (BALF).
- Neutrophil activation levels were assessed by determining the proportion of activated cells in BALF.
- Levels of anti-neutrophil cytoplasmic antibodies (ANCAs), which serve as NET-autoantibodies, were measured in the blood.
- Cholesterol content within circulating neutrophils was analyzed to examine its relationship with NET formation and disease severity.
Key Findings
- Neutrophil activation in BALF increased proportionally with the severity of equine asthma.
- Severe EA was accompanied by a disruption in local NET regulatory factors within the lungs.
- Horses with severe EA had elevated levels of circulating ANCAs, indicating a systemic autoimmune or inflammatory response related to NETs.
- Enhanced NET formation by blood neutrophils correlated with the severity of EA, suggesting systemic neutrophil activation.
- A notable decrease in cholesterol content within circulating neutrophils was observed as EA severity increased.
- The reduction in neutrophil cholesterol correlated with increased NET release and hypoxic (low oxygen) conditions.
Interpretation and Significance
- Both local (lung) and systemic (blood) changes in neutrophil function and regulation are linked to the severity of equine asthma.
- Cholesterol content in neutrophils appears to play a role in modulating NET formation and subsequent inflammation.
- Lower cellular cholesterol in neutrophils may enhance their propensity to form NETs, contributing to disease exacerbation.
- These findings suggest a previously underappreciated systemic cholesterol-associated inflammatory component that may fuel chronic inflammation and progression of EA.
- Understanding these mechanisms opens new avenues for targeted therapies aimed at modulating cholesterol metabolism or NET formation to control equine asthma severity.
Conclusion
- The study provides evidence that neutrophil extracellular trap formation and neutrophil cholesterol content are important markers and potential drivers of equine asthma severity.
- These findings highlight the interplay between systemic inflammatory responses and local lung pathology in equine asthma.
- Future research may explore therapeutic interventions aimed at cholesterol regulation or NET inhibition to alleviate EA symptoms and progression.
Cite This Article
APA
Meiseberg LK, Mergani A, Delarocque J, Imker R, Köhn D, Wanes D, Bonilla MC, Veldhuizen EJA, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N.
(2025).
Equine Asthma Is Characterised by Severity-Dependent Correlations Between Blood Neutrophil Cholesterol Content and NET Formation.
Eur J Immunol, 55(10), e70072.
https://doi.org/10.1002/eji.70072 Publication
Researcher Affiliations
- Clinic for Horses, University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Clinic for Horses, University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Section of Immunology, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
- Clinic for Horses, University of Veterinary Medicine, Hannover, Germany.
- Institute of Biochemistry, University of Veterinary Medicine, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
MeSH Terms
- Horses
- Animals
- Neutrophils / immunology
- Neutrophils / metabolism
- Asthma / immunology
- Asthma / veterinary
- Asthma / blood
- Extracellular Traps / immunology
- Extracellular Traps / metabolism
- Cholesterol / blood
- Cholesterol / metabolism
- Horse Diseases / immunology
- Horse Diseases / blood
- Bronchoalveolar Lavage Fluid / immunology
- Female
- Severity of Illness Index
- Male
Grant Funding
- University of Veterinary Medicine Hannover
- Institute of Biochemistry and the Clinic for Horses of the University of Veterinary Medicine Hannover
Conflict of Interest Statement
The authors declare no conflicts of interest.
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