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 alpha 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 alpha 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 alpha 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 alpha 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 alpha may act as a paracrine modulator of site-specific neutrophil rolling, adhesion, and exudation via mechanisms that involve the down-regulation of L-selectin.