Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome.
Abstract: Horses that develop colitis invariably exhibit signs of a systemic inflammatory response syndrome (SIRS). A significant contributor to the development of SIRS in human subjects is delayed neutrophil apoptosis, but this has not been specifically studied in horses. Objective: To determine the occurrence of ex vivo neutrophil apoptosis and its contribution to the development of SIRS in an equine colitis model. Methods: Experiment using a colitis model. Methods: Neutrophils were isolated before and after the induction of colitis using an oligofructose overdose model, placed into culture for 12 h or 24 h with or without lipopolysaccharide (LPS) at various concentrations, and assessed for the occurrence of apoptosis using Annexin V and propidium iodide staining with flow cytometric quantification. Levels of caspase-3, -8 and -9 activity were measured after 12 h of incubation in neutrophil lysates. Results: Ex vivo neutrophil apoptosis was significantly delayed in neutrophils isolated after the induction of colitis (12-h incubation: P = 0.004; 24-h incubation: P = 0.003) with concomitant reductions in caspase-3, -8 and -9 activity (caspase-3: P = 0.004; caspase-8: P = 0.02; caspase-9: P = 0.02). Neutrophils isolated after the induction of colitis were refractory to LPS-delayed apoptosis. Neutrophil apoptosis was delayed with increasing cell concentration in vitro. Conclusions: The main limitation of the study is the that the exact mechanism for delayed neutrophil apoptosis following the induction of colitis was not fully elucidated. Conclusions: The data show that neutrophil apoptosis is delayed in horses following the induction of colitis as a result of interference with the intrinsic and extrinsic apoptotic pathways, which may contribute to the development of equine SIRS. Concurrent development of neutrophilia may contribute to a prolonged neutrophil lifespan through a concentration-dependent delay in apoptosis.
© 2016 EVJ Ltd.
Publication Date: 2016-05-27 PubMed ID: 27037704DOI: 10.1111/evj.12576Google Scholar: Lookup
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- Journal Article
Summary
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This study looked into the occurrence of neutrophil apoptosis, or programmed cell death, in horses developing systemic inflammatory response syndrome (SIRS) as a result of colitis. The findings revealed delayed neutrophil apoptosis, which might contribute to the development of SIRS in horses.
Objective and Methods
- The main aim of this research was to understand the occurrence of ex vivo neutrophil apoptosis in horses and its contribution to the development of SIRS due to colitis.
- A model of colitis was induced in the horses with an overdose of oligofructose. Neutrophils, a type of white blood cell, were isolated before and after the induction of colitis.
- The isolated neutrophils were placed into culture for 12 or 24 hours, with variable amounts of lipopolysaccharide (LPS).
- The occurrence of apoptosis in these neutrophils was then determined using Annexin V and propidium iodide staining. This was quantified using flow cytometry. The activity of caspase-3, -8, and -9 were also measured after a 12-hour incubation period in neutrophil lysates.
Results
- There was a significant delay in the occurrence of ex vivo neutrophil apoptosis in neutrophils that were isolated post-induction of colitis.
- Corresponding reductions in the activity of caspase-3, -8, and -9 were observed. These enzymes are vital for the occurrence of apoptosis.
- These post-colitis neutrophils showed a decreased response to LPS-driven apoptosis delay, which indicates an altered immune response.
- A delay in neutrophil apoptosis was seen with an increase in cell concentration in vitro, indicating a concentration-dependent delay in apoptosis.
Conclusions
- The exact mechanism causing the delay in neutrophil apoptosis was not fully clarified in this study. However, it was noted that interference with the intrinsic and extrinsic apoptotic pathways could be the contributing factor.
- The data indicates that neutrophil apoptosis is delayed in horses that are induced with colitis, potentially contributing to the development of equine SIRS.
- The simultaneous development of neutrophilia, an elevated level of neutrophils, could contribute further to a prolonged neutrophil lifespan due to a concentration-dependent delay in apoptosis.
Cite This Article
APA
Anderson SL, Singh B.
(2016).
Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome.
Equine Vet J, 49(3), 383-388.
https://doi.org/10.1111/evj.12576 Publication
Researcher Affiliations
- Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
- Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
MeSH Terms
- Animals
- Apoptosis / physiology
- Colitis / chemically induced
- Colitis / metabolism
- Colitis / veterinary
- Horse Diseases / pathology
- Horses
- Neutrophils / physiology
- Oligosaccharides / toxicity
- Systemic Inflammatory Response Syndrome / veterinary
Citations
This article has been cited 8 times.- Schank N, Cottone A, Wulf M, Seiter K, Thomas B, Miller LMJ, Anderson SL, Sahyoun A, Abidi AH, Kassan M, Verma A. The Role of Short-Chain Fatty Acids (SCFAs) in Colic and Anti-Inflammatory Pathways in Horses. Animals (Basel) 2025 Dec 3;15(23).
- Koziy RV, Katselis GS, Yoshimura S, Simko E, Bracamonte JL. Temporal kinetics of serum amyloid A (SAA) concentration and identification of SAA isoforms in blood and synovial fluid of horses with experimentally induced septic arthritis, non-septic synovitis, and systemic inflammation. J Vet Diagn Invest 2025 Jan;37(1):42-54.
- Bayless RL, Sheats MK, Jones SL. Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis. Front Vet Sci 2022;9:900453.
- Camba-Gómez M, Gualillo O, Conde-Aranda J. New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation. Int J Mol Sci 2021 Mar 5;22(5).
- Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils. Front Vet Sci 2019;6:69.
- Urayama S, Arima D, Mizobe F, Shinzaki Y, Nomura M, Minamijima Y, Kusano K. Blood glucose is unlikely to be a prognostic biomarker in acute colitis with systemic inflammatory response syndrome in Thoroughbred racehorses. J Equine Sci 2018;29(1):15-19.
- Khajah MA, Ananthalakshmi KV, Edafiogho I. Anti-Inflammatory Properties of the Enaminone E121 in the Dextran Sulfate Sodium (DSS) Colitis Model. PLoS One 2016;11(12):e0168567.
- Liu YW, Yang T, Zhao L, Ni Z, Yang N, He F, Dai SS. Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome. Sci Rep 2016 Sep 20;6:33614.
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