Sheahan Breanna J, Schubert Alicia G, Schubert William, Sheats M Katie, Schnabel Lauren V, Gilbertie Jessica M
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Front Vet Sci. 2025 Feb 24;12:1512343. doi: 10.3389/fvets.2025.1512343. eCollection 2025.
Neutrophil extracellular traps (NETs) play a significant role in response to a variety of infectious and inflammatory stimuli in human and veterinary medicine. Although entrapment of bacteria can be an important function of NETs, the exuberant release of DNA and other intracellular molecules has also been negatively implicated in the pathogenesis of different diseases. Thus, NET formation must be tightly controlled and represents an opportunity for therapeutic interventions. Horses are particularly sensitive to bacterial stimuli that have previously been shown to cause NETs in other species, but the species-specific processes that control NET release have not been fully elucidated.
The purpose of this study was to compare the magnitude of response of equine neutrophils to different chemical and bacterial stimuli, including phorbol 12-myristate 13-acetate (PMA), a calcium ionophore (A23187), , and . In addition, we investigated whether ex vivo equine NET formation is controlled by the NADPH-oxidase (NOX) pathway and by autophagy, both of which control NET formation in other species.
We demonstrated that equine neutrophils produce robust NETs in response to calcium ionophore and stimuli and produce fewer NETs in response to PMA and . Both NOX-dependent and NOX-independent pathways of NET formation were identified in equine neutrophils. Autophagy inhibition altered the mechanics of NET release, by reducing the amount of extracellular DNA stranding.
These results provide insight into equine-specific neutrophil biology, which could be key for managing equine diseases such as asthma and laminitis.
中性粒细胞胞外陷阱（NETs）在人类和兽医学中对多种感染性和炎症性刺激的反应中发挥着重要作用。虽然捕获细菌可能是NETs的一项重要功能，但DNA和其他细胞内分子的过度释放也与不同疾病的发病机制存在负面关联。因此，NET的形成必须受到严格控制，这也为治疗干预提供了契机。马对先前已证明能在其他物种中引发NETs的细菌刺激特别敏感，但控制NET释放的物种特异性过程尚未完全阐明。
本研究的目的是比较马中性粒细胞对不同化学和细菌刺激的反应程度，包括佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）、钙离子载体（A₂₃₈₇）以及[此处原文缺失部分内容]。此外，我们研究了体外马NET的形成是否受烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）途径和自噬的控制，这两者在其他物种中均控制NET的形成。
我们证明马中性粒细胞对钙离子载体和[此处原文缺失部分内容]刺激产生大量NETs，而对PMA和[此处原文缺失部分内容]产生的NETs较少。在马中性粒细胞中鉴定出了NET形成的NOX依赖性和NOX非依赖性途径。自噬抑制通过减少细胞外DNA链的数量改变了NET释放的机制。
这些结果为马特异性中性粒细胞生物学提供了见解，这可能是管理马类疾病如哮喘和蹄叶炎的关键。
