B6

Metabolic and cytoskeletal control of neutrophil swarming and cluster formation

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Neutrophil swarming and cluster formation are essential for containing tissue lesions during inflammation and infections. Many individual neutrophils concentrate their combined effector functions around damaged tissue. Swarming results from a coordinated sequence of cellular responses. We revealed glycogenolysis as a metabolic pathway for the release of the swarming mediator leukotriene B4 (LTB4). Thus, the sequential steps of the swarming cascade appear to be under differential metabolic control. Based on this hypothesis, we visualise glycogen deposits in neutrophils to assess metabolic states and investigate the mechanistic interplay between glycogen regulation and LTB4 synthesis. Additionally, we establish setups for the study of cytoskeletal and metabolic adaptation processes in three-dimensional neutrophil clusters. Finally, we determine the influence of cell crowding on the neutrophil phenotype. Our future findings should prove useful for modulating neutrophil swarming and clustering responses on the metabolic level.

 

Team

Publications

Neutrophil trapping and nexocytosis, mast cell-mediated processes for inflammatory signal relay

Mihlan, M.; Wissmann, S.; Gavrilov, A.; Kaltenbach, L.; Britz, M.; Franke, K.; Hummel, B.; Imle, A.; Suzuki, R.; Stecher, M.; Glaser, K. M.; Lorentz, A.; Carmeliet, P.; Yokomizo, T.; Hilgendorf, I.; Sawarkar, R.; Diz-Muñoz, A.; Buescher, J. M.; Mittler, G.; Maurer, M.; Krause, K.; Babina, M.; Erpenbeck, L.; Frank, M.; Rambold, A. S.; Lämmermann, T.

2024 Cell