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J Appl Physiol 82: 644-651, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 82, No. 2, pp. 644-651, February 1997
CELLULAR ASPECTS OF LUNG FUNCTION

Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury

Philip C. Ridings1, Sharon Holloway2, Geoffrey L. Bloomfield1, M. L. Phillips3, Bernard J. Fisher4, Charles R. Blocher1, Harvey J. Sugerman1, and Alpha A. Fowler III4

1 Department of Surgery, 2 Department of Pediatrics, and 4 Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298; and 3 Cytel, San Diego, California 92121

Received 11 December 1995; accepted in final form 18 September 1996.

Ridings, Philip C., Sharon Holloway, Geoffrey L. Bloomfield, M. L. Phillips, Bernard J. Fisher, Charles R. Blocher, Harvey J. Sugerman, and Alpha A. Fowler III. Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury. J. Appl. Physiol. 82(2): 644-651, 1997.---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 (12 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.

adult respiratory distress syndrome; septic shock; cellular adhesion molecules

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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