Abstract
CD34+/CD133+- cells are a bone marrow derived stem cell population, which presumably contain vascular progenitor cells and are associated with improved vascular repair. In this study, we investigated whether the adhesion molecules ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular adhesion molecule-1), E-selectin und L-selectin, which are involved in homing of vascular stem cells, are upregulated by CD34+/CD133+-stem cells from septic patients and would be associated with improved clinical outcome. Peripheral blood mononuclear cells from intensive care unit (ICU) patients with (n = 30) and without sepsis (n = 10), and healthy volunteers (n = 15) were isolated using Ficoll density gradient centrifugation. The expression of VCAM-1, ICAM-1, E-selectin and L-selectin was detected on CD34+/CD133+-stem cells by flow cytometry. The severity of disease was assessed by the Simplified Acute Physiology Score (SAPS) II. Serum concentrations of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2 were determined by Enzyme-linked immunosorbent assay. The expression of VCAM-1, ICAM-1, E-selectin and L-selectin by CD34+/CD133+-stem cells was significantly upregulated in septic patients, and correlated with sepsis severity. Furthermore, high expression of VCAM-1 by CD34+/CD133+-stem cells revealed a positive association with mortalitiy (p<0.05). Furthermore, significantly higher serum concentrations of VEGF and Ang-2 were found in septic patients, however none showed a strong association with survival. Our data suggest, that VCAM-1 upregulation on CD34+/CD133+-stem cells could play a crucial role in their homing in the course of sepsis. An increase in sepsis severity resulted in both and increase in CD34+/CD133+-stem cells and VCAM-1-expression by those cells, which might reflect an increase in need for vascular repair.
Highlights
In the course of sepsis, altered endothelial function appears in macro- and microcirculation and contributes significantly to the development of multiple organ failure [1,2]
That CD34+/CD133+-stem cells in septic patients contain a distinct amount of additional KDR expression—as indicative of endothelial progenitor cells (EPC) -[7] and are increasingly mobilized in sepsis compared to non-septic intensive care unit (ICU) patients and healthy individuals[8]
We demonstrate that CD34+/CD133+-stem cells, which have been described to be rich in vascular progenitor cells [7], exhibited a high expression of the adhesion molecule Vascular Cell Adhesion Molecule-1 (VCAM-1) in septic patients, which revealed a positive association with sepsis mortality
Summary
In the course of sepsis, altered endothelial function appears in macro- and microcirculation and contributes significantly to the development of multiple organ failure [1,2]. Reconstitution of the endothelial layer can be initiated by the recruitment of vascular progenitor cells [3,4,5,6]. It was demonstrated, that CD34+/CD133+-stem cells in septic patients contain a distinct amount of additional KDR (vascular endothelial growth factor receptor 2) expression—as indicative of endothelial progenitor cells (EPC) -[7] and are increasingly mobilized in sepsis compared to non-septic ICU patients and healthy individuals[8]. The recruitment of vascular progenitor cells to inflammatory endothelial tissue is a complex process and involves a coordinated multi-step-process including mobilization, chemotaxis, homing and paracrine interaction with the resident cells [9]. The exact molecular mechanisms of vascular progenitor cell homing especially to sites of vascular inflammation in septic patients are still poorly understood
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