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

被引:23
作者
Ridings, PC
Holloway, S
Bloomfield, GL
Phillips, ML
Fisher, BJ
Blocher, CR
Sugerman, HJ
Fowler, AA
机构
[1] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT SURG,RICHMOND,VA 23298
[2] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298
[3] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT INTERNAL MED,RICHMOND,VA 23298
[4] CYTEL CORP,SAN DIEGO,CA 92121
关键词
adult respiratory distress syndrome; septic shock; cellular adhesion molecules;
D O I
10.1152/jappl.1997.82.2.644
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:644 / 651
页数:8
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