Relative contribution of endothelial cell and polymorphonuclear neutrophil activation in their interactions in systemic inflammatory response syndrome
X. Chen and N. V. Christou
Department of Surgery, McGill University, Royal Victoria Hospital, Montreal, Quebec.
OBJECTIVE: To examine the relative contribution of polymorphonuclear
neutrophil (PMN) vs endothelial cell (EC) activation on the adherence and
subsequent killing of ECs by PMNs. DESIGN: In vitro comparative studies of
PMN-EC adherence and cytotoxicity. SETTING: Research laboratory and the
surgical intensive care unit of a tertiary-level university hospital.
PATIENTS: Patients with systemic inflammatory response syndrome admitted to
the surgical intensive care unit and hospitalized preoperative noninfected
surgical patients. INTERVENTION: None. METHODS: Polymorphonuclear
neutrophils were isolated from 21 healthy volunteers, 22 preoperative
patients, and 30 patients from the surgical intensive care unit with
systemic inflammatory response syndrome. The PMNs were activated with
lipopolysaccharide, 100 ng/mL (Escherichia coli 0111:b4), for 40 minutes at
37 degrees C before the adherence and cytotoxicity assays. Human umbilical
vein endothelial monolayers were stimulated with tumor necrosis factor
alpha, 25 ng/mL, and interleukin 1 beta, 15 U/mL, for 3 hours. The PMNs or
EC cells were labeled with sodium chromate Cr 51 and used in a standard
adherence or killing assay as required. RESULTS: Control and preoperative
patient PMN treatment with lipopolysaccharide produced a modest increase in
adherence. The PMNs from patients with systemic inflammatory response
syndrome showed moderately increased human umbilical vein endothelial cell
adherence, and this could not be augmented further with lipopolysaccharide
stimulation. There was a marked increase in PMN adherence to EC after EC
activation in all study groups (P < .001). Similar to the adherence
data, human umbilical vein endothelial cell cytotoxicity was significantly
increased in all groups after human umbilical vein endothelial cell
activation (P < .01) but not after PMN stimulation with
lipopolysaccharide. CONCLUSION: These data suggest that stimulation of ECs
is far more important in producing increased adherence and cytotoxicity of
EC than PMN stimulation with lipopolysaccharide in all study groups.
Therapeutic efforts in patients with systemic inflammatory response
syndrome should be focused on the EC.
