SHEDDING OF L-SELECTIN AS A MECHANISM FOR REDUCED POLYMORPHONUCLEAR NEUTROPHIL EXUDATION IN PATIENTS WITH THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

Background: It has been recently shown that patients with the systemic inflammatory response syndrome (SIRS) have reduced neutrophil exudati on. Objective: To determine whether reduced neutrophil exudation, seen in patients with SIRS, is related to differential expression of cell adhesion molecules (CAMs), by studying endothelial and neutrophil CAM expression. Setting: A tertiary care surgical intensive care unit in a university teaching hospital. Design: Twenty-six patients with SIRS w ere compared with 18 healthy age-matched control subjects. Blister-typ e skin windows were created. Exudative neutrophils were harvested, and CAM expression was quantitated by using flow cytometry. Endothelial C AM expression was studied with immunohistochemical methods by using sk in biopsy specimens that were taken following subdermal injections of saline solution or tumor necrosis factor alpha. Results: Despite a sig nificant reduction in neutrophil exudation in patients, we found no di fference in the baseline expression of the endothelial intercellular a dhesion molecule 1, P-selectin, or E-selectin in patients vs that in c ontrol subjects. There was a significant increase in E-selectin staini ng in response to recombinant human tumor necrosis factor or in patien ts with SIRS, but not in control subjects. However, up-regulation of P -selectin did not occur in patients in response to recombinant human t umor necrosis factor alpha, as was observed in control subjects. L-sel ectin expression on circulating neutrophils was lower in patients than in control subjects, while soluble serum L-selectin levels were highe r. Conclusions: Alterations in neutrophil L-selectin, not endothelial CAMs, are important in decreased neutrophil exudation. Reduced levels of neutrophil L-selectin associated with increased levels of serum L-s electin in patients with SIRS suggest premature intravascular shedding of neutrophil L-selectin. This would compromise the initial interacti on between neutrophils and the endothelium, and, consequently, impede exudation.