Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis

• Published in: Critical care medicine Vol. 30; no. 8; p. 1842
• Main Authors: Ferri, Lorenzo E, Pascual, Jose, Seely, Andrew J E, Chaudhury, Prosanto, Christou, Nicolas V
• Format: Journal Article
• Language: English
• Published: United States 01.08.2002
• Subjects: Animals; Capillary Permeability - drug effects; Capillary Permeability - physiology; Cell Adhesion - drug effects; Injections, Intravenous; L-Selectin - pharmacology; L-Selectin - physiology; Leukocytes - cytology; Male; Mice; Models, Animal; Prospective Studies; Sepsis - metabolism; Sepsis - physiopathology; Sepsis - prevention & control; Solubility; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - pharmacokinetics
• ISSN: 0090-3493
• DOI: 10.1097/00003246-200208000-00028

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. Prospective, controlled animal study. Surgical research laboratory in a university hospital. Swiss white male mice weighing 25-35 g. 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. 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. 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.