Molecular mechanisms of platelet-mediated neutrophil extracellular traps formation during acute kidney injury
Final Report Abstract
In summary, we have identified a role for transcellular prostaglandin metabolism between neutrophils and platelets, mediated by metabolite shuttling via EVs and involving Cox1, which affects neutrophil recruitment and bacterial killing. These findings are of clinical importance, as the inhibition of cyclooxygenases is a common therapeutic approach for pain relief and anti-inflammatory therapy. In addition, the cyclooxygenase inhibitor acetylsalicylic acid (aspirin) is widely used for platelet inhibition in patients after cardiac bypass grafting. Thus, inhibitory effects on neutrophil recruitment may be of great importance in these patient collectives. Furthermore, the potential use of cyclooxygenase inhibitors could be of potential interest for the therapy of inflammatory disorders involving uncontrolled neutrophil recruitment and warrants further research in this field.
Publications
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GDF-15 prevents ventilator-induced lung injury by inhibiting the formation of platelet-neutrophil aggregates. Thromb Haemost. 2015 Aug;114(2):434-7
Van Aken, Hugo; Meersch, Melanie; Zarbock, Alexander; Herter, Jan; Kraft, Florian & Rossaint, Jan
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Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation. Br J Anaesth. 2015 Mar;114(3):509-19
Rossaint, J.; Berger, C.; Kraft, F.; Van Aken, H.; Giesbrecht, N. & Zarbock, A.
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Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun. 2016 Nov 15;7:13464
Rossaint, Jan; Kühne, Katharina; Skupski, Jennifer; Van Aken, Hugo; Looney, Mark R.; Hidalgo, Andres & Zarbock, Alexander
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Acute kidney injury: definition, diagnosis and epidemiology. Minerva Urol Nefrol. 2016 Feb;68(1):49-57
Gameiro, Joana; Agapito Fonseca, Jose; Jorge, Sofia & Lopes, Jose Antonio
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Platelets in Leukocyte Recruitment and Function. Cardiovasc Res. 2015 Aug 1;107(3):386-95
Rossaint, Jan; Margraf, Andreas & Zarbock, Alexander
