Espinosa Gabriel, Plaza Anita, Schenffeldt Andrés, Alarcón Pablo, Gajardo Gonzalo, Uberti Benjamín, Morán Gabriel, Henríquez Claudio
Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile.
Instituto de Medicina, Facultad de Medicina, Universidad Austral de Chile, Chile.
Vet Immunol Immunopathol. 2020 Mar;221:109975. doi: 10.1016/j.vetimm.2019.109975. Epub 2019 Nov 13.
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.
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).
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.
多形核中性粒细胞（PMN）是包括马在内的大多数哺乳动物血液中最大的白细胞群体，在许多传染病中发挥着重要的防御作用。然而，增加PMN作为抵御病原体的主要细胞亚群之一的机制也可能参与炎症调节异常状况的病理生理学过程。间充质干/基质细胞（MSCs）是一类具有调节炎症反应潜力的异质性细胞群体，已知其可与包括PMN在内的几乎所有免疫系统细胞相互作用。在本研究中，评估了马骨髓来源的MSCs对马PMN吞噬作用、活性氧（ROS）产生及中性粒细胞胞外陷阱（NETs）形成的体外调节作用。
与MSCs共培养时，未受刺激的PMN产生的ROS（2.88%±1.43）比单培养时的PMN（5.89%±2.63）少（p=0.016）。此外，与单培养的PMN相比，与MSCs共培养的PMN在佛波酯（PMA）刺激后产生的ROS仍然较少（p<0.05）。另外，发现用MSC上清液孵育可强烈抑制ROS产生（比对照少83%±6.35），而不影响吞噬作用或NETosis能力（p<0.01）。
这些结果表明马骨髓来源的MSCs对PMN呼吸爆发具有调节作用，而不损害其他重要的杀菌功能。这支持了马MSCs在以中性粒细胞为主要效应细胞的过度或持续性炎症状况中的潜在应用。
