• Eur J Trauma Emerg Surg · Feb 2020

    Increased extracellular ubiquitin in surgical wound fluid provides a chemotactic signal for myeloid dendritic cells.

    • Maximilian Leiblein, Norbert Ponelies, Theresa Johnson, Julian Marzi, Kerstin Kontradowitz, Emanuel Geiger, Ingo Marzi, and Dirk Henrich.
    • Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany. Maximilian.leiblein@kgu.de.
    • Eur J Trauma Emerg Surg. 2020 Feb 1; 46 (1): 153-163.

    PurposeMyeloid dendritic cells (MDC) decline significantly after multiple traumas which might be due to an increased migration into injured regions. Ubiquitin is released from dying cells and is increased in serum after trauma. Ubiquitin can bind to the chemokine receptor CXCR4. Thus, we hypothesized that elevated ubiquitin provides a chemotactic signal for MDC to injured regions.MethodsSurgical wound fluid (SWF) and serum from patients with mono-trauma (n = 20) were used to simulate the humoral situation in injured tissue. MDC were identified by flow cytometry. Chemotaxis was measured using transwell migration assays. Ubiquitin and CXCL12 (natural CXCR4 ligand) were determined by ELISA.ResultsMDC express CXCR4 and fluorescence-labeled ubiquitin binds to MDC. Ubiquitin exerts a dose-dependent chemotactic effect (fourfold at 100 ng/mL, p < 0.05). Ubiquitin concentration was sixfold higher in SWF (p < 0.05), whereas CXCL12 was increased in serum. MDC migration towards SWF was significantly reduced (- 40%, p < 0.05), if ubiquitin was neutralized by specific antibodies.ConclusionsUbiquitin is increased in SWF and exerts a significant chemotactic effect on MDC. This mechanism might play a role in attraction of immune cells to injured regions and might contribute to the decline of circulating MDC in multiple traumas.

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