The role, interplay and phenotypic changes of platelets in inflammation mediated organ damage.
Final Report Abstract
Inflammation is a crucial defense mechanism when it comes to the combatting of invading pathogens. Nonetheless, unhindered, overshooting inflammation can be harmful, evoking primary and secondary organ injury. Immune cell interplay is known to affect the cellular composition of many organs and their functionality but the underlying mechanisms when it comes to disease- and tissue-specific mechanisms are incompletely understood. Similarly, therapeutic approaches to target inflammation-mediated organ injury have so far been insufficiently addressed, especially when considered for secondary organ (comorbidities). Platelets, formerly regarded as mere bystanders in inflammation, do not only show changing phenotypic responses upon inflammatory stimuli but have recently been described to differentially impact and guide immune cells. Therefore, in this project I focused on A) the establishment of novel methodology for the assessment of secondary organ damage, B) the monitoring of immune cell and platelet phenotypic changes during inflammation and C) the testing of novel therapeutic opportunities targeting pro-resolution responses. Hereby, I could demonstrate that in a newly developed model of secondary organ damage during inflammatory arthritis, differential organ-specific immune cell interplay occurs together with functional impact on lung, heart and diseased joints; these alterations are targetable in an FPR1/2 tissue-specific manner. Since arthritis involves collagen-damage and reorganization, I assessed reactivity of platelets to a specific collagen-derivate. Similarly, I addressed the interplay of platelets and immune cells in more detail, utilizing depletion experiments.
Publications
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Resolution Pharmacology: a new way to control chronic diseases. 3rd Resolution Days (RSDIII), Besancon, France.
Perretti M., Chen J., Margraf A., Norling L.V. & Cooper D.
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Hypercholesterolemia promotes autoantibody production and a lupus‐like pathology via decreased DNase‐mediated clearance of DNA. Journal of Cellular and Molecular Medicine, 26(20), 5267-5276.
Dhawan, Umesh Kumar; Margraf, Andreas; Lech, Maciej & Subramanian, Manikandan
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Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes. Cells, 11(11), 1824.
Margraf, Andreas & Perretti, Mauro
