Shedding of L-selectin as a mechanism for reduced polymorphonuclear neutrophil exudation in patients with the systemic inflammatory response syndrome
S. N. McGill, N. A. Ahmed, F. Hu, R. P. Michel and N. V. Christou
Queen's University, Kingston, Ontario.
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.
SETTING: A tertiary care surgical intensive care unit in a university
teaching hospital. DESIGN: 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.
ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding
Li et al.
Blood 2006;108:2275-2279.
ABSTRACT
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Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices
Shpacovitch et al.
J. Leukoc. Biol. 2004;76:388-398.
ABSTRACT
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L-Selectin and {beta}2-Integrin Expression on Circulating Bovine Polymorphonuclear Leukocytes During Endotoxin Mastitis
Diez-Fraile et al.
J DAIRY SCI 2003;86:2334-2342.
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Soluble E-Selectin, Soluble L-Selectin and Soluble ICAM-1 in Bronchopulmonary Dysplasia, and Changes With Dexamethasone
Ballabh et al.
Pediatrics 2003;111:461-468.
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Immunologic and Hemodynamic Effects of "Low-Dose" Hydrocortisone in Septic Shock: A Double-Blind, Randomized, Placebo-controlled, Crossover Study
Keh et al.
Am. J. Respir. Crit. Care Med. 2003;167:512-520.
ABSTRACT
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A Functional Role for Circulating Mouse L-Selectin in Regulating Leukocyte/Endothelial Cell Interactions In Vivo
Tu et al.
J. Immunol. 2002;169:2034-2043.
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Inhibition of Leukocyte Rolling by Nitric Oxide during Sepsis Leads to Reduced Migration of Active Microbicidal Neutrophils
Benjamim et al.
Infect. Immun. 2002;70:3602-3610.
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Neutrophil Migration Mechanisms, with an Emphasis on the Pulmonary Vasculature
Wagner and Roth
Pharmacol. Rev. 2000;52:349-374.
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Selective Recruitment of T-Cell Subsets to the Udder during Staphylococcal and Streptococcal Mastitis: Analysis of Lymphocyte Subsets and Adhesion Molecule Expression
Soltys and Quinn
Infect. Immun. 1999;67:6293-6302.
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