Equine bone marrow-derived mesenchymal stromal cells inhibit reactive oxygen species production by neutrophils.
Abstract: Polymorphonuclear neutrophils (PMN) are the largest leukocyte population in the blood of most mammals including horses, and play an important defensive role in many infectious diseases. However, the mechanisms that increase PMN as one of the main cellular subsets in the defense against pathogens could also be involved in the pathophysiology of dysregulated inflammatory conditions. Mesenchymal stem/stromal cells (MSCs) are a heterogeneous population with a modulatory potential on the inflammatory response and are known to interact with nearly all cells of the immune system, including PMN. In this study, the in vitro modulation of equine bone marrow-derived MSCs on equine PMN phagocytosis, ROS production, and NETs generation was assessed. Results: In co-culture with MSCs, unstimulated PMN produce less ROS (2.88 % ± 1.43) than PMN in single culture (5.89 % ± 2.63) (p = 0.016). Moreover, PMN co-cultured with MSCs remain conditioned to produce fewer ROS after PMA stimulation in comparison to PMN in single culture (p < 0.05). Additionally, it was found that incubation with MSC supernatant strongly inhibited ROS production (83 % ± 6.35 less than control) without affecting phagocytosis or capacity for NETosis (p < 0.01). Conclusions: These results suggest a modulatory effect of equine BM-derived MSCs on PMN respiratory burst, without impairing other important microbicidal functions. This supports the potential use of equine MSCs in excessive or persistent inflammatory conditions in which neutrophils are the main effector cells.
Copyright © 2019. Published by Elsevier B.V.
Publication Date: 2019-11-13 PubMed ID: 32087476DOI: 10.1016/j.vetimm.2019.109975Google Scholar: Lookup
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- Journal Article
Summary
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The research article discusses how horse bone marrow-derived mesenchymal stromal cells (MSCs) can reduce the amount of reactive oxygen species (ROS) produced by neutrophils, which are a type of white blood cell. This finding suggests that horse MSCs could be beneficial in cases of extreme or chronic inflammation where neutrophils are major contributors.
Study Background
- The research focuses on Polymorphonuclear neutrophils (PMN), a type of leukocyte present in the bloodstreams of most mammals, including horses. PMNs are crucial for defense against many infectious diseases.
- However, the same pathways that bolster PMN numbers to fight pathogens could also contribute to unchecked inflammation, causing harm to the body.
- Mesenchymal stem/stromal cells (MSCs) are a diverse group of cells notable for their anti-inflammatory properties. MSCs can interact with virtually every cell type in the immune system, including PMNs.
- This study aims to analyze how horse bone marrow-derived MSCs influence the processes of PMN phagocytosis (the engulfing and destruction of pathogens), ROS production (a byproduct of PMN action that can cause damage when overproduced), and NETs generation (neutrophil extracellular traps are a defense mechanism of PMNs).
Research Findings
- The research found that when PMNs were co-cultured with MSCs, they produced significantly less ROS than PMN cultured alone. Hence, the MSCs have a modulating effect, reducing the ROS production of PMNs.
- Notably, this change in behavior remained even after stimulation with Phorbol Myristate Acetate (PMA), proving that the MSCs conditioned the PMNs to produce fewer ROS consistently.
- Furthermore, it was discovered that exposing PMNs to the supernatant of MSCs significantly inhibited ROS production without impacting their phagocytic ability or NETosis capacity–their ability to form neutrophil extracellular traps to catch and kill microbes.
Implications of the Study
- The research indicates that horse bone marrow-derived MSCs can regulate the production of ROS by PMNs without negatively impacting their function. This implies that they may be able to maintain the essential defense capabilities of neutrophils while curbing their harmful overactivity.
- Given these results, MSCs could be a potential therapeutic treatment in excessive or chronic inflammation conditions where neutrophils are primarily responsible. This opens a new possibility for managing inflammation-related conditions in veterinary medicine.
Cite This Article
APA
Espinosa G, Plaza A, Schenffeldt A, Alarcón P, Gajardo G, Uberti B, Morán G, Henríquez C.
(2019).
Equine bone marrow-derived mesenchymal stromal cells inhibit reactive oxygen species production by neutrophils.
Vet Immunol Immunopathol, 221, 109975.
https://doi.org/10.1016/j.vetimm.2019.109975 Publication
Researcher Affiliations
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: essgabo@gmail.com.
- Instituto de Medicina, Facultad de Medicina, Universidad Austral de Chile, Chile. Electronic address: anitaplazaflores@yahoo.com.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: schenffeldt-andres@hotmail.cl.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: pabloalarcon.u@gmail.com.
- Escuela de Graduados, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: gonzalo.gajardo@uach.cl.
- Instituto de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: benjamin.uberti@uach.cl.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: gmoran@uach.cl.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile. Electronic address: claudio.henriquez@uach.cl.
MeSH Terms
- Animals
- Bone Marrow Cells / cytology
- Cells, Cultured
- Coculture Techniques
- Female
- Horses
- Male
- Mesenchymal Stem Cells / cytology
- Neutrophils / immunology
- Neutrophils / metabolism
- Phagocytosis
- Reactive Oxygen Species / metabolism
- Respiratory Burst / immunology
- Tetradecanoylphorbol Acetate / pharmacology
Conflict of Interest Statement
Declaration of Competing Interest The authors declare that they have no competing interests.
Citations
This article has been cited 11 times.- Soukup R, Gerner I, Mohr T, Gueltekin S, Grillari J, Jenner F. Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction. Int J Mol Sci 2023 Jun 29;24(13).
- Stope MB. The Connection between Immunocompetence and Reproduction in Wildlife. Life (Basel) 2023 Mar 14;13(3).
- Uberti B, Plaza A, Henríquez C. Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species. Front Vet Sci 2022;9:806069.
- Franck T, Ceusters J, Graide H, Mouithys-Mickalad A, Serteyn D. Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase. Cells 2021 Dec 10;10(12).
- Armitage JD, Tan DBA, Sturm M, Moodley YP. Transcriptional profiling of circulating mononuclear cells from patients with chronic obstructive pulmonary disease receiving mesenchymal stromal cell infusions. Stem Cells Transl Med 2021 Nov;10(11):1470-1481.
- van de Vyver M, Powrie YSL, Smith C. Targeting Stem Cells in Chronic Inflammatory Diseases. Adv Exp Med Biol 2021;1286:163-181.
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals (Basel) 2021 Jan 19;11(1).
- Ellison-Hughes GM, Colley L, O'Brien KA, Roberts KA, Agbaedeng TA, Ross MD. The Role of MSC Therapy in Attenuating the Damaging Effects of the Cytokine Storm Induced by COVID-19 on the Heart and Cardiovascular System. Front Cardiovasc Med 2020;7:602183.
- Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, Morán G, Plaza A, Henríquez C. Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity. Front Vet Sci 2020;7:318.
- Salinas-Varas C, Espinosa G, Muñoz-Caro T, Conejeros I, Gärtner U, Fey K, Arnhold S, Taubert A, Hermosilla C. Equine adipose-derived stem cells modulate in vitro neutrophil extracellular trap release by polymorphonuclear neutrophils. Front Vet Sci 2025;12:1685757.
- Zegallai HM, Abu-El-Rub E, Olayinka-Adefemi F, Cole LK, Sparagna GC, Marshall AJ, Hatch GM. Tafazzin deficiency in mouse mesenchymal stem cells promote reprogramming of activated B lymphocytes toward immunosuppressive phenotypes. FASEB J 2022 Aug;36(8):e22443.
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