EXPRESSION OF HUMAN NEUTROPHIL L-SELECTIN DURING THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME IS PARTLY MEDIATED BY TUMOR-NECROSIS-FACTOR-ALPHA

Background: Rolling of neutrophils on the vascular endothelium is a re quisite 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-ma tched control subjects and to determine whether tumor necrosis factor a modulates L-selectin expression on human neutrophils. Setting: A ter tiary care surgical intensive care unit at a university teaching hospi tal. Subjects: Patients identified with SIRS (American College of Crit ical Care Physicians and Society of Critical Care Medicine criteria) w ere compared with healthy age-matched control subjects. Venous blood s amples that were obtained from healthy laboratory control subjects wer e used to examine the time course of L-selectin expression. Main Outco me Measures: Neutrophil L-selectin expression was determined by flow c ytometry in patients with SIRS and control subjects. Tumor necrosis fa ctor alpha concentrations were determined in blood and exudative fluid from patients with SIRS. Neutrophil L-selectin expression was measure d during a 45-minute time course in the presence of recombinant human tumor necrosis factor alpha and N-formyl-methionyl-leucyl-phenylalanin e. Results: Circulating neutrophils from patients with SIRS had signif icantly less L-selectin expression than did control subjects. Tumor ne crosis factor alpha at concentrations similar to those found in exudat ive fluid caused a dose- and time-dependent decrease in neutrophil L-s electin expression. Conclusion: Tumor necrosis factor alpha may act as a paracrine modulator of site-specific neutrophil rolling, adhesion, and exudation via mechanisms that involve the down-regulation of L-sel ectin.