The protective role of a synthetic sialylated oligosaccharide in
sepsis-induced acute lung injury.
Ridings, Philip C, Sharon Holloway, Geoffrey L Bloomfield, Ml
Phillips, Bernard J Fisher, Charles R Blocher, Harvey J Sugerman,
Alpha A Fowler.
Departments of Surgery, Pediatrics and Internal Medicine, Medical
College of Virginia, Virginia Commonwealth University, Richmond, VA,
and Cytel Corporation, San Diego, CA
APStracts 3:0470A, 1996.
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 Lewisx are proposed to act as these
counterreceptors. We studied the effects of a synthetic Sialyl Lewisx
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) prior to sepsis, followed by continuous
infusion of CY-1503 (12 mg/kg/hr). 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 to controls. This study suggest
blockade of selectin interactions as a potential therapeutic
intervention in sepsis-induced lung injury.
Received 11 December 1995; accepted in final form 18 September
1996.
APS Manuscript Number A1289-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996