Circulating endothelial cells in patients with septic shock

The Vascular endothelium has a central role in the control of microvascular tone, and it has been proposed that vascular endothelial damage occurs in septic shock, producing multiorgan failure. We have developed a method of d etecting circulating endothelial cells (EC) that provides direct evidence o f EC shedding in human sepsis. Human umbilical vein endothelial cells (HUVE C) were seeded in whole blood and recovered by isopycnic centrifugation to validate the technique. Blood samples were subsequently taken from 11 healt hy volunteers, nine ventilated intensive care unit (ICU) control patients w ithout sepsis, eight patients with sepsis but without shock, and 15 patient s with septic shock. EC were identified by indirect immunofluorescence, usi ng antibodies to von Willebrand factor (vWf) and the vascular endothelial g rowth factor receptor KDR. Mean HUVEC recovery was 86% for 20 to 100 seeded cells/ml of blood. vWf-positive EC counts per milliliter were significantl y higher (analysis of variance [ANOVA], p < 0.0001) in patients with sepsis (16.1 +/- 2.7 [mean +/- SEM]) and septic shock (30.1 +/- 3.3) than in heal thy (1.9 +/- 0.5) or ICU controls (2.6 +/- 0.6). KDR-positive EC counts per milliliter were also significantly higher (ANOVA, p < 0.0001) in patients with sepsis (4.2 +/- 1.1/ml) and septic shock (10.4 +/- 1.2/ml) than in hea lthy (0.7 +/- 0.3/ml) or ICU controls (0.5 +/- 0.2/ml). Cell counts made wi th anti-vWf antibody were consistently higher than those made with anti KDR antibody, but correlation between the two counts was high (r(2) = 0.93). T he number of circulating KDR-positive EC was significantly higher in patien ts who died of septic shock than in survivors (12.0 +/- 1.6/ml Versus 7.1 /- 1.2/ml, p = 0.026). An increase in circulating EC can be identified duri ng sepsis and septic shock. This supports the hypothesis that endothelial d amage occurs in human sepsis.