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doi:10.22028/D291-44169
Titel: | Microvascular Mechanisms of Polyphosphate-Induced Neutrophil-Endothelial Cell Interactions in vivo |
VerfasserIn: | Du, Feifei Wang, Yongzhi Ding, Zhiyi Laschke, Matthias W. Thorlacius, Henrik |
Sprache: | Englisch |
Titel: | European Surgical Research |
Bandnummer: | 60 |
Heft: | 1-2 |
Seiten: | 53-62 |
Verlag/Plattform: | Karger |
Erscheinungsjahr: | 2019 |
Freie Schlagwörter: | Endothelium Inflammation Leukocyte Transmigration |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Background: Polyphosphates (PolyPs) have been reported to exert pro-inflammatory effects. However, the molecular mechanisms regulating PolyP-provoked tissue accumulation of leukocytes are not known. The aim of the present investigation was to determine the role of specific adhesion molecules in PolyP-mediated leukocyte recruitment. Methods: PolyPs and TNF-α were intrascrotally administered, and anti-P-selectin, anti-E-selectin, anti-P-selectin glycoprotein ligand-1 (PSGL-1), anti-membrane-activated complex-1 (Mac-1), antilymphocyte function antigen-1 (LFA-1), and neutrophil depletion antibodies were injected intravenously or intraperitoneally. Intravital microscopy of the mouse cremaster microcirculation was used to examine leukocyte-endothelium interactions and recruitment in vivo. Results: Intrascrotal injection of PolyPs increased leukocyte accumulation. Depletion of neutrophils abolished PolyP-induced leukocyte-endothelium interactions, indicating that neutrophils were the main leukocyte subtype responding to PolyP challenge. Immunoneutralization of P-selectin and PSGL-1 abolished PolyP-provoked neutrophil rolling, adhesion, and emigration. Moreover, immunoneutralization of Mac-1 and LFA-1 had no impact on neutrophil rolling but markedly reduced neutrophil adhesion and emigration evoked by PolyPs. Conclusion: These results suggest that P-selectin and PSGL-1 exert important roles in PolyP-induced inflammatory cell recruitment by mediating neutrophil rolling. In addition, our data show that Mac-1 and LFA-1 are necessary for supporting PolyP-triggered firm adhesion of neutrophils to microvascular endothelium. These novel findings define specific molecules as potential targets for pharmacological intervention in PolyP-dependent inflammatory diseases. |
DOI der Erstveröffentlichung: | 10.1159/000497435 |
URL der Erstveröffentlichung: | https://doi.org/10.1159/000497435 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-441697 hdl:20.500.11880/39503 http://dx.doi.org/10.22028/D291-44169 |
ISSN: | 1421-9921 0014-312X |
Datum des Eintrags: | 28-Jan-2025 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Chirurgie |
Professur: | M - Prof. Dr. Michael D. Menger |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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