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Home / Equine Research Bank / Front Vet Sci / Equine neutrophils selectively release neutrophil extracellu...
Frontiers in veterinary science2025; 12; 1512343; doi: 10.3389/fvets.2025.1512343

Equine neutrophils selectively release neutrophil extracellular traps in response to chemical and bacterial agonists.

Abstract: Neutrophil extracellular traps (NETs) play a significant role in response to a variety of infectious and inflammatory stimuli in human and veterinary medicine. Although entrapment of bacteria can be an important function of NETs, the exuberant release of DNA and other intracellular molecules has also been negatively implicated in the pathogenesis of different diseases. Thus, NET formation must be tightly controlled and represents an opportunity for therapeutic interventions. Horses are particularly sensitive to bacterial stimuli that have previously been shown to cause NETs in other species, but the species-specific processes that control NET release have not been fully elucidated. Unassigned: The purpose of this study was to compare the magnitude of response of equine neutrophils to different chemical and bacterial stimuli, including phorbol 12-myristate 13-acetate (PMA), a calcium ionophore (A23187), Staphylococcus aureus, and Escherichia coli. In addition, we investigated whether ex vivo equine NET formation is controlled by the NADPH-oxidase (NOX) pathway and by autophagy, both of which control NET formation in other species. Unassigned: We demonstrated that equine neutrophils produce robust NETs in response to calcium ionophore and E. coli stimuli and produce fewer NETs in response to PMA and S. aureus. Both NOX-dependent and NOX-independent pathways of NET formation were identified in equine neutrophils. Autophagy inhibition altered the mechanics of NET release, by reducing the amount of extracellular DNA stranding. Unassigned: These results provide insight into equine-specific neutrophil biology, which could be key for managing equine diseases such as asthma and laminitis.
Copyright © 2025 Sheahan, Schubert, Schubert, Sheats, Schnabel and Gilbertie.
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Publication Date: 2025-02-24 PubMed ID: 40066197PubMed Central: PMC11891193DOI: 10.3389/fvets.2025.1512343Google Scholar: Lookup
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  • Journal Article

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.

This study focuses on understanding the response of equine neutrophils to chemical and bacterial stimuli, especially their production of neutrophil extracellular traps (NETs), which play crucial roles in resisting infectious and inflammatory stimuli and are associated with several diseases.

Study Objective and Methods

  • The research aimed to examine equine neutrophils’ sensitivity and response magnitudes to various stimuli, such as chemicals (phorbol 12-myristate 13-acetate and a calcium ionophore) and bacteria, functioning aspects not fully understood previously.
  • They also explored whether ex-vivo equine NET formation is regulated by the NADPH-oxidase (NOX) pathway and autophagy, critical controls for extracellular trap generation in other species.

Main Findings

  • The researchers discovered that the equine neutrophils significantly generate NETs in reaction to calcium ionophore and other bacterial stimuli, while they release fewer NETs in response to PMA.
  • Two pathways relating to NET formation were identified, including both NOX-dependent and NOX-independent routes, indicating flexibility in the neutrophils’ immune response.
  • It was found that inhibiting autophagy can alter NET release mechanics, notably causing a reduction in the amount of extracellular DNA stranding.

Significance of the Results

  • The study’s results shed light on the unique biology of equine neutrophils. This could be instrumental in understanding and managing equine diseases such as asthma and laminitis.
  • Understanding the mechanisms underlying NETs could open up avenues for new therapeutic interventions where the regulation of neutrophil activity is required.
  • The discovery of both NOX-dependent and NOX-independent pathways indicates multiple routes of immune defense, potentially allowing effective reactions to a wider variety of stimuli.

Cite This Article

APA
Sheahan BJ, Schubert AG, Schubert W, Sheats MK, Schnabel LV, Gilbertie JM. (2025). Equine neutrophils selectively release neutrophil extracellular traps in response to chemical and bacterial agonists. Front Vet Sci, 12, 1512343. https://doi.org/10.3389/fvets.2025.1512343

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 12
Pages: 1512343

Researcher Affiliations

Sheahan, Breanna J
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Schubert, Alicia G
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Schubert, William
  • College of William & Mary, Williamsburg, VA, United States.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Schnabel, Lauren V
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Gilbertie, Jessica M
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States.

Grant Funding

  • T35 OD011070 / NIH HHS

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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