Calcium ionophore-activated platelets induce eosinophil extracellular trap formation

Abstract

Background: 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 be-tween 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 extra-cellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers.Methods: Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned me-dium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation.Results: 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.Conclusions: Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation.& COPY; 2022 Japanese Society of Allergology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).