PROTECTIVE ROLE OF SYNTHETIC SIALYLATED OLIGOSACCHARIDE IN SEPSIS-INDUCED ACUTE LUNG INJURY

Proper engagement of leukocyte and endothelial cell selectins with the ir counterreceptors is an initial step in neutrophil trafficking to si tes of inflammation. Certain fucosylated carbohydrate determinants suc h 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 ex perimental gram-negative sepsis. Anesthetized ventilated swine were ma de 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 (12 mg . kg(-1). h(-1)). Tr eatment with CY-1503 did not prevent the development of pulmonary hype rtension, systemic hypotension, decline in cardiac output, or severe n eutropenia. However, CY-1503 significantly attenuated lung injury, dem onstrated by decreased bronchoalveolar lavage protein content and neut rophil influx, lowered lung myeloperoxidase activity, and improved art erial oxygenation. Neutrophils from septic and CY-1503 animals showed significant activation, reflected by upregulated CD18 expression and p riming for oxidant burst compared with control animals. This study sug gests blockade of selectin interactions as a potential therapeutic int ervention in sepsis-induced lung injury.