title: Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis.
abstract: 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.
authors.affiliation: Department of Surgery and Microbiology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Lorenzo E
authors.initials: LE
authors.lastname: Ferri
authors.forename: Jose
authors.initials: J
authors.lastname: Pascual
authors.forename: Andrew J E
authors.initials: AJ
authors.lastname: Seely
authors.forename: Prosanto
authors.initials: P
authors.lastname: Chaudhury
authors.forename: Nicolas V
authors.initials: NV
authors.lastname: Christou
mesh_terms: 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*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin