VCAM-1 expression is upregulated by CD34+/CD133+-stem cells derived from septic patients

PLoS One. 2018 Mar 30;13(3):e0195064. doi: 10.1371/journal.pone.0195064. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen / metabolism*
  • Adult
  • Antigens, CD34 / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sepsis / blood
  • Sepsis / metabolism*
  • Sepsis / pathology*
  • Stem Cells / metabolism*
  • Survival Analysis
  • Up-Regulation*
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • Vascular Endothelial Growth Factor A / blood
  • Vesicular Transport Proteins / blood

Substances

  • AC133 Antigen
  • Antigens, CD34
  • VPS51 protein, human
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Vesicular Transport Proteins

Grants and funding

Christian Patry and Neysan Rafat have been granted a 2 year research scholarship by the University of Heidelberg (physician scientist program). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.