Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis.
OBJECTIVE
We have previously demonstrated that leukocyte delivery to remote sites is decreased in sepsis and that increased concentrations of soluble L-selectin are, in part, responsible for this finding. Given that leukocytes have been implicated in the pathogenesis of vascular leakage, we hypothesized that the elevated soluble L-selectin concentrations in sepsis may translate into decreased inflammation-mediated leukocyte-endothelial cell interactions and vascular leakage at these sites.


METHODS
Prospective, controlled animal study.


METHODS
Surgical research laboratory in a university hospital.


METHODS
Swiss white male mice weighing 25-35 g.


METHODS
Mice were randomized to one of three study groups: intracremaster tumor necrosis factor-alpha with subsequent intravenous bicarbonate buffered solution; intracremaster tumor necrosis factor-alpha with intravenous soluble L-selectin (10 microg/mL); and intracremaster bicarbonate buffered solution with intravenous bicarbonate buffered solution. The cremaster muscle was prepared for both light and fluorescence intravital microscopy 2 hrs after intracremaster injection, and fluorescein isothiocyanate-labeled albumin was injected intravenously. Leukocyte-endothelial interactions (rolling flux, rolling velocity, and adherence) were counted off-line. Postcapillary venule leakage was determined by the permeability index (perivenular/intravenular fluorescence) after intravenous injection of fluorescent albumin.


RESULTS
Soluble L-selectin significantly attenuated tumor necrosis factor-alpha-mediated increases in leukocyte adherence and vascular leakage. Leukocyte rolling velocity was restored to baseline with soluble L-selectin; however, rolling flux was not altered. Blood pressure, shear rate, and leukocyte counts did not differ between groups.


CONCLUSIONS
Soluble L-selectin decreases local inflammation-mediated leukocyte adherence and vascular leakage in vivo. The increased concentrations of soluble L-selectin in sepsis may represent a protective mechanism by which the host attempts to diminish the deleterious systemic effects of activated leukocytes during sepsis.
Ferri
Lorenzo E
LE
Department of Surgery and Microbiology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Pascual
Jose
J
Seely
Andrew J E
AJ
Chaudhury
Prosanto
P
Christou
Nicolas V
NV
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D007275:Injections, Intravenous; D019041:L-Selectin / Q000494:pharmacology* / Q000502:physiology; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000493:pharmacokinetics*
D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin