The role, interplay and phenotypic changes of platelets in inflammation mediated organ damage.

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A well-balanced inflammatory reaction allows the body to defend itself against external pathogens, whereas an overshooting inflammatory response can harm the organism itself. Such uncontrolled inflammatory response can be observed in septic patients and to a lesser extent also in arthritis patients. Herein, the recruitment and unhindered activation of inflammatory cells and breaking of the endothelial barrier lead to not only local inflammatory complications, such as edema formation or joint destruction, but due to a systemic overshooting inflammatory response also to secondary (remote) organ damage. Importantly, any inflammatory response must be terminated and resolved to prevent ongoing organ damage. Platelets have been found to affect acute onset of arthritis as well as acute lung injury, but little is known about the resolution potential of platelets, changes in platelet and macrophage phenotypes, impact of such on recruitment of inflammatory cells and the role of platelet-microparticles in mediation of secondary organ dysfunction. Interestingly, platelet-microparticles have been found to directly mediate local inflammation but dissemination of platelet-microparticles to remote regions within the body has also been discovered, detecting these particles in lymph and bone marrow during arthritis. This project aims to elucidate underlying mechanisms of platelet-mediated inflammation and resolution of inflammatory processes as well as the impact of microparticles on secondary organ damage, inflammation, and resolution. Of special interest, interplay of platelets with macrophages, which are known to be main contributors to both inflammation and cell-clearance during resolution, and phenotypic changes will be examined in different disease models and organs. As inflammatory conditions such as arthritis, colitis and sepsis are common clinical morbidities resulting in high hospital expenditures and mortality rates, advancing the understanding of regulatory mechanisms of inflammation, secondary organ damage and resolution of such is of utmost importance for translational endeavors.