Tamoxifen induces apoptotic neutrophil efferocytosis in horses.
Abstract: Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.
Publication Date: 2018-01-02 PubMed ID: 29297134DOI: 10.1007/s11259-017-9709-6Google Scholar: Lookup
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- Journal Article
Summary
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The research focuses on the effects of the drug Tamoxifen on a process called efferocytosis in horses, implying that the drug could potentially alleviate conditions like equine asthma by promoting the removal of harmful neutrophils from the system.
Overview of the Research
- The study delves into the role of macrophages and neutrophils, vital cellular elements involved in acute inflammation and its subsequent resolution. These cells are noted to play significant roles in the winding down of chronic, adaptive inflammatory processes.
- Exaggerated neutrophil activity can be detrimental to surrounding tissues and critical in numerous diseases such as allergic asthma and chronic obstructive pulmonary disease in humans, and in equine asthma (also known as recurrent airway obstruction (RAO).
- The non-steroidal estrogen receptor modulator, Tamoxifen (TX), is found to have effects on cell growth and survival, and has been previously observed to stimulate early apoptosis (programmed cell death) of blood and bronchoalveolar lavage fluid (BALF) neutrophils in horses with acute pulmonary inflammation. This induced early apoptosis leads to a reduction in BALF neutrophils and an improvement in the clinical condition of the animals.
Purpose and Methods of the Study
- The study aims to determine whether TX stimulates efferocytosis, an important biological process where apoptotic cells are removed by phagocytic cells, of neutrophils by alveolar macrophages in vitro i.e., in a controlled environment outside a living organism.
- The researchers carried out an efferocytosis assay, myeloperoxidase (MPO) detection, and translocation phosphatidylserine (PS) on neutrophils collected from the peripheral blood samples of five healthy horses. MPO is an enzyme stored in neutrophils indicating cellular activity, while PS is a phospholipid typically facing the inside of the cell, and translocation to the outside is a signal for phagocytic cells to begin efferocytosis.
Study Findings and Conclusion
- The study found that TX treatment increases efferocytosis of peripheral neutrophils by alveolar macrophages in in vitro samples from healthy horses.
- There was also an observed increase in MPO concentration and PS translocation in TX-treated neutrophils when compared to control cells.
- From these results, the researchers concluded that Tamoxifen has a direct effect on equine peripheral blood neutrophils by promoting the engulfment of apoptotic neutrophils by alveolar macrophages, thus facilitating the clearance of these potentially harmful cells from the system.
Cite This Article
APA
Olave C, Morales N, Uberti B, Henriquez C, Sarmiento J, Ortloff A, Folch H, Moran G.
(2018).
Tamoxifen induces apoptotic neutrophil efferocytosis in horses.
Vet Res Commun, 42(1), 57-63.
https://doi.org/10.1007/s11259-017-9709-6 Publication
Researcher Affiliations
- Department of Pharmacology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
- Department of Pharmacology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
- Department of Clinical Veterinary Sciences, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
- Department of Pharmacology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
- Department of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
- College of Veterinary Medicine, Universidad Catolica de Temuco, Temuco, Chile.
- Department of Immunology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
- Department of Pharmacology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile. gmoran@uach.cl.
MeSH Terms
- Animals
- Apoptosis / drug effects
- Estrogen Antagonists / pharmacology
- Horses
- Macrophages / drug effects
- Neutrophils / drug effects
- Phagocytosis / drug effects
- Tamoxifen / pharmacology
Grant Funding
- 1160352 / Fondecyt
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Citations
This article has been cited 7 times.- Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G. Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses.. Front Vet Sci 2022;9:1025249.
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