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 exudation.


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.


METHODS
A tertiary care surgical intensive care unit in a university teaching hospital.


METHODS
Twenty-six patients with SIRS were compared with 18 healthy age-matched control subjects. Blister-type skin windows were created. Exudative neutrophils were harvested, and CAM expression was quantitated by using flow cytometry. Endothelial CAM expression was studied with immunohistochemical methods by using skin biopsy specimens that were taken following subdermal injections of saline solution or tumor necrosis factor alpha.


RESULTS
Despite a significant reduction in neutrophil exudation in patients, we found no difference in the baseline expression of the endothelial intercellular adhesion molecule 1, P-selectin, or E-selectin in patients vs that in control subjects. There was a significant increase in E-selectin staining in response to recombinant human tumor necrosis factor alpha in patients with SIRS, but not in control subjects. However, up-regulation of P-selectin did not occur in patients in response to recombinant human tumor necrosis factor alpha, as was observed in control subjects. L-selectin expression on circulating neutrophils was lower in patients than in control subjects, while soluble serum L-selectin levels were higher.


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-selectin in patients with SIRS suggest premature intravascular shedding of neutrophil L-selectin. This would compromise the initial interaction between neutrophils and the endothelium, and, consequently, impede exudation.
Queen's University, Kingston, Ontario.
S N
SN
McGill
N A
NA
Ahmed
F
F
Hu
R P
RP
Michel
N V
NV
Christou
D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D019040:E-Selectin / Q000032:analysis / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000032:analysis / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin