RELATIVE CONTRIBUTION OF ENDOTHELIAL-CELL AND POLYMORPHONUCLEAR NEUTROPHIL ACTIVATION IN THEIR INTERACTIONS IN SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

Objective: To examine the relative contribution of polymorphonuclear n eutrophil (PMN) vs endothelial cell (EC) activation on the adherence a nd subsequent killing of ECs by PMNs. Design: In vitro comparative stu dies of PMN-EC adherence and cytotoxicity. Setting: Research laborator y and the surgical intensive care unit of a tertiary-level university hospital. Patients: Patients with systemic inflammatory response syndr ome admitted to the surgical intensive care unit and hospitalized preo perative noninfected surgical patients. Intervention: None. Methods: P olymorphonuclear 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:b 4), for 40 minutes at 37 degrees C before the adherence and cytotoxici ty assays. Human umbilical vein endothelial monolayers were stimulated with tumor necrosis factor alpha, 25 ng/mL, and interleukin 1 beta, 1 5 U/mL, for 3 hours. The PMNs or EC cells were labeled with sodium chr omate Cr 51 and used in a standard adherence or killing assay as requi red. Results: Control and preoperative patient PMN treatment with lipo polysaccharide produced a modest increase in adherence. The PMNs from patients with systemic inflammatory response syndrome showed moderatel y increased human umbilical vein endothelial cell adherence, and this could not be augmented further with lipopolysaccharide stimulation. Th ere was a marked increase in PMN adherence to EC after EC activation i n all study groups (P<.001). Similar to the adherence data, human umbi lical vein endothelial cell cytotoxicity was significantly increased i n all groups after human umbilical vein endothelial cell activation (P <.01) but not after PMN stimulation with lipopolysaccharide. Conclusio n: These data suggest that stimulation of ECs is far more important in producing increased adherence and cytotoxicity of EC than PMN stimula tion with lipopolysaccharide in all study groups. Therapeutic efforts in patients with systemic inflammatory response syndrome should be foc used on the EC.