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...

Verfasser: Wolf, Marc
Joseph, Robiya
Austermann, Judith
Scharrnbeck-Davis, Chiara
Hermann, Sven
Roth, Johannes
Vogl, Thomas
FB/Einrichtung:FB 13: Biologie
FB 05: Medizinische Fakultät
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2023
Publikation in MIAMI:30.11.2023
Datum der letzten Änderung:30.11.2023
Angaben zur Ausgabe:[Electronic ed.]
Quelle:Biomedicines 11 (2023) 3, 835, 1-22
Schlagwörter:calprotectin; cytoskeleton; integrin; leukocyte; migration
Fachgebiet (DDC):610: Medizin und Gesundheit
Lizenz:CC BY 4.0
Sprache:English
Förderung:Finanziert durch den Open-Access-Publikationsfonds der Universität Münster.
Format:PDF-Dokument
URN:urn:nbn:de:hbz:6-68938614588
Weitere Identifikatoren:DOI: 10.17879/88938482644
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-68938614588
Verwandte Dokumente:
Onlinezugriff:10.3390_biomedicines11030835.pdf
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520 3 |a 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. 
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