Monika Pruenster, Roland Immler, Jonas Roth, Tim Kuchler, Thomas Bromberger, Matteo Napoli, Katrin Nussbaumer, Ina Rohwedder, Lou Martha Wackerbarth, Chiara Piantoni, Konstantin Hennis, Diana Fink, Sebastian Kallabis, Tobias Schroll, Sergi Masgrau-Alsina, Agnes Budke, Wang Liu, Dietmar Vestweber, Christian Wahl-Schott, Johannes Roth, Felix Meissner, Markus Moser, Thomas Vogl, Veit Hornung, Petr Broz & Markus Sperandio
Together with colleagues from Munich, Münster, Bonn and Lausanne (Switzerland), the PILOT researchers Roland Immler and Markus Sperandio have recently published a paper in Nature Immunology.
In this work, they demonstrate that pro-inflammatory S100A8/A9 (also known as calprotectin or MRP8/14) is released from neutrophils in an NLRP3 inflammasome dependent fashion. Engagement with endothelial expressed E-selectin during intravascular rolling activates the NLRP3 protein complex in neutrophils within minutes resulting in GSDMD pore formation and ensuing release of cytosolic small alarmins, among them S100A8/A9. This rapid mode of inflammasome activation involves the activation of the voltage-gated potassium channel KV1.3 and Bruton’s tyrosine kinase (Btk). Interestingly, the researchers demonstrated that E-selectin triggered pore formation is a transient and reversible process preventing unwanted cell death of neutrophils within the blood stream.
