Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells
Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their...
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| Format: | Article |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.866938/full |
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| author | Alexander Kogel Sven Fikenzer Luisa Uhlmann Lena Opitz Jasmin M. Kneuer Karl Georg Haeusler Matthias Endres Matthias Endres Jürgen Kratzsch Viktoria Schwarz Christian Werner Hermann Kalwa Susanne Gaul Ulrich Laufs |
| author_facet | Alexander Kogel Sven Fikenzer Luisa Uhlmann Lena Opitz Jasmin M. Kneuer Karl Georg Haeusler Matthias Endres Matthias Endres Jürgen Kratzsch Viktoria Schwarz Christian Werner Hermann Kalwa Susanne Gaul Ulrich Laufs |
| author_sort | Alexander Kogel |
| collection | DOAJ |
| description | Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known.Methods: We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 h before, immediately after, and again 24–58 h after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells.Results: Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (+52% compared with the baseline, p < 0.05) and a decrease during the follow-up after 24–58 h (12% reduction compared with immediately after the run, p < 0.01). Confocal microscopy revealed that human endothelial cells can internalize extracellular NLRP3 inflammasome particles. After internalization, endothelial cells showed an inflammatory response with a higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p < 0.05) and increased adhesion of monocytes (1.5-fold, p < 0.05).Conclusion: These findings identify extracellular inflammasome particles as novel systemic mediators of cell–cell communication that are transiently increased after acute extensive exercise with a high mechanical muscular load. |
| first_indexed | 2024-12-12T16:10:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T16:10:38Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ba6b22b190094126ac823d68befe72aa2022-12-22T00:19:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-05-011310.3389/fphys.2022.866938866938Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial CellsAlexander Kogel0Sven Fikenzer1Luisa Uhlmann2Lena Opitz3Jasmin M. Kneuer4Karl Georg Haeusler5Matthias Endres6Matthias Endres7Jürgen Kratzsch8Viktoria Schwarz9Christian Werner10Hermann Kalwa11Susanne Gaul12Ulrich Laufs13Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyDepartment of Neurology, Universitätsklinikum Würzburg, Würzburg, GermanyDepartment of Neurology and Center for Stroke Research Berlin, Charité—Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Neurodegenerative Diseases (DZNE) and German Centre for Cardiovascular Research (DZHK), Berlin, GermanyInstitute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, GermanyDepartment for Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University, Saarbrücken, GermanyDepartment for Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University, Saarbrücken, GermanyRudolf-Boehm-Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Universität Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, GermanyObjectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known.Methods: We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 h before, immediately after, and again 24–58 h after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells.Results: Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (+52% compared with the baseline, p < 0.05) and a decrease during the follow-up after 24–58 h (12% reduction compared with immediately after the run, p < 0.01). Confocal microscopy revealed that human endothelial cells can internalize extracellular NLRP3 inflammasome particles. After internalization, endothelial cells showed an inflammatory response with a higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p < 0.05) and increased adhesion of monocytes (1.5-fold, p < 0.05).Conclusion: These findings identify extracellular inflammasome particles as novel systemic mediators of cell–cell communication that are transiently increased after acute extensive exercise with a high mechanical muscular load.https://www.frontiersin.org/articles/10.3389/fphys.2022.866938/fullmarathonNLRP3inflammasomecardiovascular diseaseendothelial dysfunctioninflammation |
| spellingShingle | Alexander Kogel Sven Fikenzer Luisa Uhlmann Lena Opitz Jasmin M. Kneuer Karl Georg Haeusler Matthias Endres Matthias Endres Jürgen Kratzsch Viktoria Schwarz Christian Werner Hermann Kalwa Susanne Gaul Ulrich Laufs Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells Frontiers in Physiology marathon NLRP3 inflammasome cardiovascular disease endothelial dysfunction inflammation |
| title | Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells |
| title_full | Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells |
| title_fullStr | Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells |
| title_full_unstemmed | Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells |
| title_short | Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells |
| title_sort | extracellular inflammasome particles are released after marathon running and induce proinflammatory effects in endothelial cells |
| topic | marathon NLRP3 inflammasome cardiovascular disease endothelial dysfunction inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.866938/full |
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