Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents.
Abstract: Mast cells are known for their detrimental effects in various inflammatory conditions. Regimens that induce selective mast cell apoptosis may therefore be of therapeutic significance. Earlier studies have demonstrated that murine- and human-cultured mast cells are highly sensitive to apoptosis induced by the lysosomotropic agent LeuLeuOMe (LLME). However, the efficacy of lysosomotropic agents for inducing apoptosis of in vivo-derived airway mast cells and the impact on mast cells in other species have not been assessed. Here we addressed whether lysosomotropic agents can induce cell death of equine in vivo-derived mast cells. Bronchoalveolar lavage (BAL) fluids from horses were incubated with LLME at 15-100 μm for up to 48 h. The overall cell viability was unaffected by 15 μm LLME up to 48 h, whereas a relatively modest drop in total cell counts (~30%) was seen at the highest LLME dose used. In contrast to the relatively low effect on total cell counts, LLME efficiently and dose dependently reduced the number of mast cells in BAL fluids, with an almost complete depletion (96%) of mast cells after 24 h of incubation with 100 μm LLME. A significant but less dramatic reduction (up to ~45%) of lymphocytes was also seen, whereas macrophages and neutrophils were essentially resistant. The appearance of apoptotic bodies suggested a mechanism involving apoptosis rather than necrosis. These findings suggest that equine airway mast cells are highly sensitive to lysosomotropic agents. Possibly, lysosomotropic agents could be of therapeutic value to treat disorders involving harmful accumulation of mast cells in the airways.
© 2016 The Foundation for the Scandinavian Journal of Immunology.
Publication Date: 2016-11-04 PubMed ID: 27808429DOI: 10.1111/sji.12502Google 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
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 research investigates the effects of lysosomotropic agents, particularly LeuLeuOMe (LLME), on mast cells in horses, with findings suggesting that these agents could potentially be used in therapies for inflammatory conditions caused by harmful accumulation of mast cells. It reveals that equine mast cells are highly sensitive to apoptosis induced by LLME, thereby reducing the overall concentration of these cells in horse’s bronchoalveolar lavage (BAL) fluids.
Mast Cells and Inflammatory Conditions
- Mast cells have been widely associated with various inflammatory conditions due to their detrimental effects.
- Therapies that can selectively induce mast cell apoptosis, or cell death, could therefore have significant medical value in the treatment of these conditions.
Lysosomotropic Agents and Apoptosis
- Previous studies have shown that mast cells cultured from both mice and humans are highly sensitive to apoptosis induced by a lysosomotropic agent called LeuLeuOMe (LLME).
- The susceptibility of in vivo-derived airway mast cells to lysosomotropic agents and the impact of these agents on mast cells in other species hadn’t been explored prior to this study.
Testing on Equine Mast Cells
- The researchers in this study sought to establish whether lysosomotropic agents can cause cell death in horse-derived mast cells.
- Bronchoalveolar lavage (BAL) fluids from horses were treated with LLME at concentrations ranging from 15-100μm for up to 48 hours.
- Results showed that treatment with 15μm LLME did not affect overall cell viability up to 48 hours. However, at the highest dose used, there was a small decline in total cell numbers (~30%).
Impact on Mast Cells and Other Cells
- LLME was found to significantly and dose-dependently reduce the number of mast cells in the BAL fluids. Almost all mast cells (96%) were depleted after 24 hours of incubation with 100μm LLME.
- A notable but less significant reduction of lymphocytes was seen, reaching up to 45%. In contrast, macrophages and neutrophils were largely unaffected.
- The occurrence of apoptotic bodies implies that the cell death mechanism involved was apoptosis rather than necrosis.
Implications of the Findings
- The research findings suggest that equine airway mast cells are highly sensitive to lysosomotropic agents, with the potential for LLME to selectively reduce their numbers.
- These agents could potentially have therapeutic value in treating conditions involving the harmful buildup of mast cells in the airways, although further research is required to confirm and explore this potential.
Cite This Article
APA
Wernersson S, Riihimäki M, Pejler G, Waern I.
(2016).
Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents.
Scand J Immunol, 85(1), 30-34.
https://doi.org/10.1111/sji.12502 Publication
Researcher Affiliations
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Clinical Sciences, Section of Large Animal Surgery and Medicine, Equine Internal Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
MeSH Terms
- Animals
- Apoptosis / drug effects
- Bronchoalveolar Lavage Fluid / cytology
- Bronchoalveolar Lavage Fluid / immunology
- Cell Survival
- Cells, Cultured
- Dipeptides / pharmacology
- Dipeptides / therapeutic use
- Horse Diseases / drug therapy
- Horses
- Humans
- Hypersensitivity / drug therapy
- Lymphocytes / immunology
- Lysosomes / drug effects
- Mast Cells / drug effects
- Mice
- Respiratory Tract Diseases / drug therapy
- Respiratory Tract Diseases / veterinary
Citations
This article has been cited 2 times.- Akula S, Riihimäki M, Waern I, Åbrink M, Raine A, Hellman L, Wernersson S. Quantitative Transcriptome Analysis of Purified Equine Mast Cells Identifies a Dominant Mucosal Mast Cell Population with Possible Inflammatory Functions in Airways of Asthmatic Horses.. Int J Mol Sci 2022 Nov 12;23(22).
- Amini Pouya M, Afshani SM, Maghsoudi AS, Hassani S, Mirnia K. Classification of the present pharmaceutical agents based on the possible effective mechanism on the COVID-19 infection.. Daru 2020 Dec;28(2):745-764.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
