Histamine plays a central role in various allergic diseases, such as allergic asthma and allergic rhinitis. Neutrophil extracellular traps (NETs) formation is a novel effector mechanism of neutrophils to defend against various stimuli. In this present study, we aimed to investigate the role of histamine on bovine NET formation, and examined its preliminary molecular mechanisms. Cell Counting Kit-8 (CCK8) and Lactate dehydrogenase assays showed that histamine had no significant influence on PMNs (polymorphonuclear leukocytes) viability. Confocal microscopy analyses identified NET structures by co-localizing the main components of NETs, and NET quantification revealed that histamine-triggered NETs were released in a dose-dependent manner. Furthermore, we found reactive oxygen species (ROS) production, phosphorylated extracellular signal-regulated kinase (ERK) and p38 proteins were significantly elevated in histamine-challenged PMNs. By applying functional inhibitors of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), ERK and p38, histamine-triggered NETs were markedly reduced, indicating their importance in histamine-triggered NET formation. Our findings described histamine-triggered NET formation, and revealed its potential molecular mechanisms via NADPH oxidase, ERK and p38 pathways. This is the first study to depict histamine-triggered NET formation, which could provide a new insight into histamine-related diseases.

组胺在各种过敏性疾病中起着核心作用，例如过敏性哮喘和过敏性鼻炎。中性粒细胞胞外陷阱 (NETs) 的形成是中性粒细胞抵御各种刺激的一种新型效应机制。在本研究中，我们旨在研究组胺对牛 NET 形成的作用，并检查其初步分子机制。Cell Counting Kit-8 (CCK8) 和乳酸脱氢酶测定表明组胺对 PMN（多形核白细胞）活力没有显着影响。共聚焦显微镜分析通过共定位 NET 的主要成分来识别 NET 结构，NET 量化显示组胺触发的 NET 以剂量依赖性方式释放。此外，我们发现活性氧 (ROS) 的产生，磷酸化的细胞外信号调节激酶 (ERK) 和 p38 蛋白在组胺攻击的 PMN 中显着升高。通过应用烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH 氧化酶）、ERK 和 p38 的功能抑制剂，组胺触发的 NET 显着减少，表明它们在组胺触发的 NET 形成中的重要性。我们的研究结果描述了组胺触发的 NET 形成，并通过 NADPH 氧化酶、ERK 和 p38 途径揭示了其潜在的分子机制。这是第一项描述组胺触发的 NET 形成的研究，可以为组胺相关疾病提供新的见解。组胺触发的 NET 显着减少，表明它们在组胺触发的 NET 形成中的重要性。我们的研究结果描述了组胺触发的 NET 形成，并通过 NADPH 氧化酶、ERK 和 p38 途径揭示了其潜在的分子机制。这是第一项描述组胺触发的 NET 形成的研究，可以为组胺相关疾病提供新的见解。组胺触发的 NET 显着减少，表明它们在组胺触发的 NET 形成中的重要性。我们的研究结果描述了组胺触发的 NET 形成，并通过 NADPH 氧化酶、ERK 和 p38 途径揭示了其潜在的分子机制。这是第一项描述组胺触发的 NET 形成的研究，可以为组胺相关疾病提供新的见解。