Department of BionanoTechnology, Hanyang University, Ansan, South Korea.
Department of Molecular and Life Sciences, College of Science and Convergence Technology, Hanyang University, Ansan, South Korea.
Allergol Int. 2023 Jul;72(3):466-476. doi: 10.1016/j.alit.2022.12.002. Epub 2022 Dec 29.
Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers.
Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned medium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation.
The CM and pellet from A23187-activated platelets stimulated eosinophils to generate EET, whereas those from thrombin- or ADP-activated platelets failed to induce such generation. The EET-inducing activity of the A23187-activated platelet culture was linearly proportional to the number of activated platelets. Interestingly, while EET formation induced by the direct stimulation of eosinophils with A23187 was NADPH oxidase (NOX)-dependent, EET formation induced by A23187-activated platelets was NOX-independent and significantly inhibited by necroptosis pathway inhibitors.
Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation.
血小板在炎症反应中发挥调节作用，通过分泌大量颗粒并在激活时崩解为膜结合的微颗粒。推测嗜酸性粒细胞和血小板之间的相互作用与过敏性气道炎症的病理学有关。在这项研究中，我们研究了活化的血小板是否可以诱导嗜酸性粒细胞细胞外陷阱（EET）的形成，这是一种激活的嗜酸性粒细胞释放网状 DNA 纤维的细胞过程。
用钙离子载体 A23187 和血小板激动剂凝血酶和二磷酸腺苷（ADP）刺激血小板。将血小板培养物分成条件培养基（CM）和沉淀，然后将其覆盖在嗜酸性粒细胞上，以检查 EET 的形成。
A23187 激活的血小板的 CM 和沉淀可刺激嗜酸性粒细胞产生 EET，而凝血酶或 ADP 激活的血小板则不能诱导这种生成。A23187 激活血小板培养物的 EET 诱导活性与激活的血小板数量呈线性比例。有趣的是，虽然用 A23187 直接刺激嗜酸性粒细胞诱导的 EET 形成依赖于 NADPH 氧化酶（NOX），但 A23187 激活的血小板诱导的 EET 形成不依赖于 NOX，并被坏死性凋亡途径抑制剂显著抑制。
活化的血小板及其产物可能诱导 EET 的形成，从而增强它们在嗜酸性粒细胞性气道炎症中的作用。
