Expression of human neutrophil L-selectin during the systemic inflammatory response syndrome is partly mediated by tumor factor alpha
N. A. Ahmed, J. Yee, B. Giannias, B. Kapadia and N. V. Christou
Department of Royal Surgery, Royal Victoria Hospital, McGill University, Montreal, Quebec.
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.
