Equine bone marrow-derived mesenchymal stromal cells inhibit reactive oxygen species production by neutrophils
Gabriel Espinosa1, Anita Plaza2, Andrés Schenffeldt1
1Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile.
Background:
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.
Insights
Equine mesenchymal stem/stromal cells (MSCs) modulate neutrophil function by reducing reactive oxygen species (ROS) production without impairing microbicidal activity. This suggests MSCs could treat inflammatory conditions involving neutrophils.
Area of Science:
- Immunology
- Stem Cell Biology
- Veterinary Medicine
Background:
- Polymorphonuclear neutrophils (PMNs) are key immune cells in horses, crucial for fighting infections but also implicated in inflammatory diseases.
- Mesenchymal stem/stromal cells (MSCs) possess immunomodulatory properties and interact with immune cells, including PMNs.
Purpose of the Study:
- To investigate the in vitro effects of equine bone marrow-derived MSCs on equine PMN functions.
- To assess the impact of MSCs on PMN phagocytosis, reactive oxygen species (ROS) production, and neutrophil extracellular trap (NET) generation.
Main Methods:
- Equine bone marrow-derived MSCs were co-cultured with equine PMNs.
- Assessed PMN phagocytosis, ROS production, and NETosis in single cultures, co-cultures, and with MSC supernatant.
- Statistical analysis was performed to determine significance.
Main Results:
- Co-culture with MSCs significantly reduced ROS production in unstimulated and stimulated PMNs.
- MSC supernatant strongly inhibited PMN ROS production by 83% without affecting phagocytosis or NETosis.
- PMN ROS production was significantly lower in co-culture with MSCs compared to single culture.
Conclusions:
- Equine MSCs modulate PMN respiratory burst activity, specifically reducing ROS production.
- This modulation occurs without compromising essential microbicidal functions like phagocytosis and NETosis.
- Equine MSCs show potential for therapeutic use in managing inflammatory conditions where neutrophils play a significant role.
