A7

Metabolite-driven neutrophil dysfunction in sterile and non-sterile inflammation

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Selected metabolites can regulate neutrophil functions in inflammation. Based on our preliminary data, we further explore the effects of soluble uric acid, an endogenous suppressor of neutrophil activation and migration, as well as the pro-inflammatory role of crystalline cholesterol, a known trigger of arterial immunothrombosis, in cholesterol crystal embolism-related kidney infarction and organ failure. We examine the impact of soluble uric acid on neutrophil function during non-sterile inflammation, e.g., in infection, and assess the effects of urate-lowering therapies and antibiotic-mediated suppression of the intestinal microbiota. In addition, we study the effects of soluble uric acid on neutrophils and platelets in immunothrombosis following non-sterile inflammation, as in infection and sterile inflammation, as in ischemic kidney infarction. Finally, we focus on the interplay between neutrophils and platelets during sterile inflammation, as in ischemic kidney infarction, namely, pyroptotic cell death and the cell type-specific contribution of gasdermin D in neutrophils versus platelets, in continuation of our previous work.

Team

Publications

Inhibition of Complement Factor C5a or C5aR for Cholesterol Crystal Embolism-Related Vascular Thrombosis with Microvascular Injury and Its Consequences

Zhao, D.; Han, C.; Mammadova-Bach, E.; Watanabe-Kusunoki, K.; Honda, T. S. B.; Li, Y.; Li, C.; Li, Q.; Long, H.; Lyubenov, L.; Shi, C.; Santovito, D.; Weber, C.; Boor, P.; Droste, P.; Parikh, S.; Shapiro, J.; Chiara, L. D.; Carangelo, G.; Romagnani, P.; Klussmann, S.; Vater, A.; Anders, H.-J.

2024 Kidney Int

Neutrophils - Biology and Diversity

Maier-Begandt, D.; Alonso-Gonzalez, N.; Klotz, L.; Erpenbeck, L.; Jablonska, J.; Immler, R.; Hasenberg, A.; Mueller, T. T.; Herrero-Cervera, A.; Aranda-Pardos, I.; Flora, K.; Zarbock, A.; Brandau, S.; Schulz, C.; Soehnlein, O.; Steiger, S.; the TRR332 consortium.

2023 Nephrol Dial Transplant