title: Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury.
abstract: Proper engagement of leukocyte and endothelial cell selectins with their counterreceptors is an initial step in neutrophil trafficking to sites of inflammation. Certain fucosylated carbohydrate determinants such as sialyl Lewis-x are proposed to act as these counterreceptors. We studied the effects of a synthetic sialyl Lewis-x analog, CY-1503, on the course of hemodynamic derangements and acute lung injury during experimental gram-negative sepsis. Anesthetized ventilated swine were made septic with an infusion of live Pseudomonas aeruginosa. A treatment group received an initial bolus of CY-1503 (60 mg/kg) before sepsis, followed by continuous infusion of CY-1503 (15 mg.kg-1.h-1). Treatment with CY-1503 did not prevent the development of pulmonary hypertension, systemic hypotension, decline in cardiac output, or severe neutropenia. However, CY-1503 significantly attenuated lung injury, demonstrated by decreased bronchoalveolar lavage protein content and neutrophil influx, lowered lung myeloperoxidase activity, and improved arterial oxygenation. Neutrophils from septic and CY-1503 animals showed significant activation, reflected by upregulated CD18 expression and priming for oxidant burst compared with control animals. This study suggests blockade of selectin interactions as a potential therapeutic intervention in sepsis-induced lung injury.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Ridings
authors.forename: S
authors.initials: S
authors.lastname: Holloway
authors.forename: G L
authors.initials: GL
authors.lastname: Bloomfield
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: B J
authors.initials: BJ
authors.lastname: Fisher
authors.forename: C R
authors.initials: CR
authors.lastname: Blocher
authors.forename: H J
authors.initials: HJ
authors.lastname: Sugerman
authors.forename: A A
authors.initials: AA
authors.lastname: Fowler
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury; D009844:Oligosaccharides / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy; D013552:Swine; D013997:Time Factors
chemical_list: D009844:Oligosaccharides