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

European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society
Maximilian LeibleinDirk Henrich

Abstract

Myeloid 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. Surgical 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. MDC 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. Ubiquitin 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 contribut...Continue Reading

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