Bibliographic Details
| Title: |
Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes |
| Authors: |
Antonella Russo, Hendrik Schürmann, Matthias Brandt, Katja Scholz, Anna Livia L. Matos, David Grill, Julian Revenstorff, Maximilian Rembrink, Meike von Wulffen, Lena Fischer‐Riepe, Peter J. Hanley, Hans Häcker, Monika Prünster, Francisco Sánchez‐Madrid, Sven Hermann, Luisa Klotz, Volker Gerke, Timo Betz, Thomas Vogl, Johannes Roth |
| Source: |
Advanced Science, Vol 9, Iss 36, Pp n/a-n/a (2022) |
| Publisher Information: |
Wiley, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Science |
| Subject Terms: |
alarmin, calprotectin, CD69, MRP8/MRP14, migration, S100A8/S100A9 tetramer, Science |
| More Details: |
Abstract Mechanisms keeping leukocytes distant of local inflammatory processes in a resting state despite systemic release of inflammatory triggers are a pivotal requirement for avoidance of overwhelming inflammation but are ill defined. Dimers of the alarmin S100A8/S100A9 activate Toll‐like receptor‐4 (TLR4) but extracellular calcium concentrations induce S100A8/S100A9‐tetramers preventing TLR4‐binding and limiting their inflammatory activity. So far, only antimicrobial functions of released S100A8/S100A9‐tetramers (calprotectin) are described. It is demonstrated that extracellular S100A8/S100A9 tetramers significantly dampen monocyte dynamics as adhesion, migration, and traction force generation in vitro and immigration of monocytes in a cutaneous granuloma model and inflammatory activity in a model of irritant contact dermatitis in vivo. Interestingly, these effects are not mediated by the well‐known binding of S100A8/S100A9‐dimers to TLR‐4 but specifically mediated by S100A8/S100A9‐tetramer interaction with CD69. Thus, the quaternary structure of these S100‐proteins determines distinct and even antagonistic effects mediated by different receptors. As S100A8/S100A9 are released primarily as dimers and subsequently associate to tetramers in the high extracellular calcium milieu, the same molecules promote inflammation locally (S100‐dimer/TLR4) but simultaneously protect the wider environment from overwhelming inflammation (S100‐tetramer/CD69). |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2198-3844 |
| Relation: |
https://doaj.org/toc/2198-3844 |
| DOI: |
10.1002/advs.202201505 |
| Access URL: |
https://doaj.org/article/436a845c56a94e71958ce48320f05a72 |
| Accession Number: |
edsdoj.436a845c56a94e71958ce48320f05a72 |
| Database: |
Directory of Open Access Journals |
