S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes
Immune reactions are characterized by the rapid immigration of phagocytes into sites of inflammation. Meticulous regulation of these migratory processes is crucial for preventing uncontrolled and harmful phagocyte extravasation. S100A8/S100A9 is the major calcium-binding protein complex expressed in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/3/835 |
| _version_ | 1797613316602855424 |
|---|---|
| author | Marc Wolf Robiya Joseph Judith Austermann Chiara Scharrnbeck-Davis Sven Hermann Johannes Roth Thomas Vogl |
| author_facet | Marc Wolf Robiya Joseph Judith Austermann Chiara Scharrnbeck-Davis Sven Hermann Johannes Roth Thomas Vogl |
| author_sort | Marc Wolf |
| collection | DOAJ |
| description | Immune reactions are characterized by the rapid immigration of phagocytes into sites of inflammation. Meticulous regulation of these migratory processes is crucial for preventing uncontrolled and harmful phagocyte extravasation. S100A8/S100A9 is the major calcium-binding protein complex expressed in phagocytes. After release, this complex acts as a proinflammatory alarmin in the extracellular space, but the intracellular functions of these highly abundant proteins are less clear. Results of this study reveal an important role of S100A8/S100A9 in coordinated cytoskeleton rearrangement during migration. We found that S100A8/S100A9 was able to cross-link F-actin and microtubules in a calcium- and phosphorylation-dependent manner. Cells deficient in S100A8/S100A9 showed abnormalities in cell adhesion and motility. Missing cytoskeletal interactions of S100A8/S100A9 caused differences in the surface expression and activation of β1-integrins as well as in the regulation of Src/Syk kinase family members. Loss of S100A8/S100A9 led to dysregulated integrin-mediated adhesion and migration, resulting in an overall higher dynamic activity of non-activated S100A8/S100A9-deficient phagocytes. Our data suggest that intracellular S100A8/S100A9 is part of a novel regulatory mechanism that ensures the precise control necessary to facilitate the change between the quiescent and activated state of phagocytes. |
| first_indexed | 2024-03-11T06:53:12Z |
| format | Article |
| id | doaj.art-127d921d3de74c3a8bdf9b3b18af137d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:12Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-127d921d3de74c3a8bdf9b3b18af137d2023-11-17T09:46:19ZengMDPI AGBiomedicines2227-90592023-03-0111383510.3390/biomedicines11030835S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of LeukocytesMarc Wolf0Robiya Joseph1Judith Austermann2Chiara Scharrnbeck-Davis3Sven Hermann4Johannes Roth5Thomas Vogl6Institute of Immunology, University of Münster, 48149 Münster, GermanyDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas, Houston, TX 77030, USAInstitute of Immunology, University of Münster, 48149 Münster, GermanyInstitute of Immunology, University of Münster, 48149 Münster, GermanyEuropean Institute for Molecular Imaging, University of Münster, 48149 Münster, GermanyInstitute of Immunology, University of Münster, 48149 Münster, GermanyInstitute of Immunology, University of Münster, 48149 Münster, GermanyImmune reactions are characterized by the rapid immigration of phagocytes into sites of inflammation. Meticulous regulation of these migratory processes is crucial for preventing uncontrolled and harmful phagocyte extravasation. S100A8/S100A9 is the major calcium-binding protein complex expressed in phagocytes. After release, this complex acts as a proinflammatory alarmin in the extracellular space, but the intracellular functions of these highly abundant proteins are less clear. Results of this study reveal an important role of S100A8/S100A9 in coordinated cytoskeleton rearrangement during migration. We found that S100A8/S100A9 was able to cross-link F-actin and microtubules in a calcium- and phosphorylation-dependent manner. Cells deficient in S100A8/S100A9 showed abnormalities in cell adhesion and motility. Missing cytoskeletal interactions of S100A8/S100A9 caused differences in the surface expression and activation of β1-integrins as well as in the regulation of Src/Syk kinase family members. Loss of S100A8/S100A9 led to dysregulated integrin-mediated adhesion and migration, resulting in an overall higher dynamic activity of non-activated S100A8/S100A9-deficient phagocytes. Our data suggest that intracellular S100A8/S100A9 is part of a novel regulatory mechanism that ensures the precise control necessary to facilitate the change between the quiescent and activated state of phagocytes.https://www.mdpi.com/2227-9059/11/3/835calprotectincytoskeletonintegrinleukocytemigration |
| spellingShingle | Marc Wolf Robiya Joseph Judith Austermann Chiara Scharrnbeck-Davis Sven Hermann Johannes Roth Thomas Vogl S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes Biomedicines calprotectin cytoskeleton integrin leukocyte migration |
| title | S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes |
| title_full | S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes |
| title_fullStr | S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes |
| title_full_unstemmed | S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes |
| title_short | S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes |
| title_sort | s100a8 s100a9 integrates f actin and microtubule dynamics to prevent uncontrolled extravasation of leukocytes |
| topic | calprotectin cytoskeleton integrin leukocyte migration |
| url | https://www.mdpi.com/2227-9059/11/3/835 |
| work_keys_str_mv | AT marcwolf s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT robiyajoseph s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT judithaustermann s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT chiarascharrnbeckdavis s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT svenhermann s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT johannesroth s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes AT thomasvogl s100a8s100a9integratesfactinandmicrotubuledynamicstopreventuncontrolledextravasationofleukocytes |