Abstract
BackgroundEndothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome.MethodsPeripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and − 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays.ResultsEPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival.ConclusionsOur data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis.
Highlights
Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival
These findings indicate, that the stromal cell derived factor 1α (SDF-1α)/CXC-motivechemokine receptor 4 (CXCR-4) signalling might be involved in EPC mediated regenerative processes during sepsis
A positive correlation of vascular endothelial growth factor (VEGF), Angiopoietin 2 (Ang2) and stromal cell-derived factor (SDF)-1α with EPC levels in septic patients compared to controls in our study indicates an impact of those factors on mobilization of EPC from the bone marrow during sepsis as shown before [34, 45,46,47]
Summary
Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. Endothelial progenitor cells (EPC) might constitute a potential targeted treatment option in the future It could be demonstrated, that EPC have the potential to regenerate and reconstitute damaged endothelial layers in several diseases like sepsis and acute respiratory distress syndrome (ARDS) [3,4,5,6,7]. We and Endothelial progenitor cells are able to migrate into damaged subendothelial layers, subsequently promote angiogenesis and induce endothelial barrier regeneration, especially in states of systemic endothelial inflammation [3]. This sequence must be preceded by a directed EPC homing process [11]. Similar to leukocyte homing EPC homing is a coordinated multi-step-process
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