title: Circulating endothelial progenitor cells are not affected by acute systemic inflammation.
abstract: Vascular injury causes acute systemic inflammation and mobilizes endothelial progenitor cells (EPCs) and endothelial cell (EC) colony-forming units (EC-CFUs). Whether such mobilization occurs as part of a nonspecific acute phase response or is a phenomenon specific to vascular injury remains unclear. We aimed to determine the effect of acute systemic inflammation on EPCs and EC-CFU mobilization in the absence of vascular injury. Salmonella typhus vaccination was used as a model of acute systemic inflammation. In a double-blind randomized crossover study, 12 healthy volunteers received S. typhus vaccination or placebo. Phenotypic EPC populations enumerated by flow cytometry [CD34(+)VEGF receptor (VEGF)R-2(+)CD133(+), CD14(+)VEGFR-2(+)Tie2(+), CD45(-)CD34(+), as a surrogate for late outgrowth EPCs, and CD34(+)CXCR-4(+)], EC-CFUs, and serum cytokine concentrations (high sensitivity C-reactive protein, IL-6, and stromal-derived factor-1) were quantified during the first 7 days. Vaccination increased circulating leukocyte (9.8 + or - 0.6 vs. 5.1 + or - 0.2 x 10(9) cells/l, P < 0.0001), serum IL-6 [0.95 (0-1.7) vs. 0 (0-0) ng/l, P = 0.016], and VEGF-A [60 (45-94) vs. 43 (21-64) pg/l, P = 0.006] concentrations at 6 h and serum high sensitivity C-reactive protein at 24 h [2.7 (1.4-3.6) vs. 0.4 (0.2-0.8) mg/l, P = 0.037]. Vaccination caused a 56.7 + or - 7.6% increase in CD14(+) cells at 6 h (P < 0.001) and a 22.4 + or - 6.9% increase in CD34(+) cells at 7 days (P = 0.04). EC-CFUs, putative vascular progenitors, and the serum stromal-derived factor-1 concentration were unaffected throughout the study period (P > 0.05 for all). In conclusion, acute systemic inflammation causes nonspecific mobilization of hematopoietic progenitor cells, although it does not selectively mobilize putative vascular progenitors. We suggest that systemic inflammation is not the primary stimulus for EPC mobilization after acute vascular injury.
authors.affiliation: Centre for Cardiovascular Science, Univ. of Edinburgh, Chancellor's Bldg., Edinburgh EH16 4SU, UK. gareth.padfield@nhs.net
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Padfield
authors.forename: Olga
authors.initials: O
authors.lastname: Tura
authors.forename: Marlieke L A
authors.initials: ML
authors.lastname: Haeck
authors.forename: Abigail
authors.initials: A
authors.lastname: Short
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Freyer
authors.forename: G Robin
authors.initials: GR
authors.lastname: Barclay
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D022562:Salmonella Vaccines / Q000009:adverse effects*; D012485:Salmonella typhi
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D022562:Salmonella Vaccines; D002097:C-Reactive Protein
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