Expression of Human Neutrophil L-Selectin During the Systemic Inflammatory Response Syndrome Is Partly Mediated by Tumor Necrosis Factor α

Abstract
Background: Rolling of neutrophils on the vascular endothelium is a requisite step to transmigration to areas of infection or inflammation, and this is regulated in part by the neutrophil cell adhesion molecule l-selectin. Objectives: To compare l-selectin expression in patients with systemic inflammatory response syndrome (SIRS) and healthy age-matched control subjects and to determine whether tumor necrosis factor α modulates l-selectin expression on human neutrophils. Setting: A tertiary care surgical intensive care unit at a university teaching hospital. Subjects: Patients identified with SIRS (American College of Critical Care Physicians and Society of Critical Care Medicine criteria) were compared with healthy age-matched control subjects. Venous blood samples that were obtained from healthy laboratory control subjects were used to examine the time course of l-selectin expression. Main Outcome Measures: Neutrophil l-selectin expression was determined by flow cytometry in patients with SIRS and control subjects. Tumor necrosis factor α concentrations were determined in blood and exudative fluid from patients with SIRS. Neutrophil l-selectin expression was measured during a 45-minute time course in the presence of recombinant human tumor necrosis factor α and N-formyl-methionyl-leucyl-phenylalanine. Results: Circulating neutrophils from patients with SIRS had significantly less l-selectin expression than did control subjects. Tumor necrosis factor α at concentrations similar to those found in exudative fluid caused a dose-and time-dependent decrease in neutrophil l-selectin expression. Conclusion: Tumor necrosis factor α may act as a paracrine modulator of site-specific neutrophil rolling, adhesion, and exudation via mechanisms that involve the down-regulation of l-selectin. (Arch Surg. 1996;131:31-36)