Sialyl Lewisx-containing oligosaccharide exerts beneficial effects in murine traumatic shock.

Abstract

We investigated the effects of a soluble sialyl Lewisx-containing oligosaccharide (SLex-OS) in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, a survival time of 85 +/- 15 min, significant increases in ileal myeloperoxidase (P < 0.01), and plasma free amino-nitrogen activities (P < 0.01). Treatment with SLex-OS (10 mg/kg) 10 min posttrauma prolonged survival time to 198 +/- 29 min (P < 0.01), significantly attenuated ileal myeloperoxidase activity (P < 0.01), and diminished the accumulation of plasma free amino-nitrogen (P < 0.01), drug vs. vehicle, respectively. Furthermore, endothelium-dependent relaxation to acetylcholine in superior mesenteric artery rings isolated from SLex-OS-treated shock rats was significantly preserved (70 +/- 6 vs. 40 +/- 5% relaxation). No beneficial effects were observed using a nonfucosylated control oligosaccharide. Moreover, addition of SLex-OS significantly inhibited unstimulated human polymorphonuclear neutrophil (PMN) adherence in vitro to trauma-activated superior mesenteric artery endothelium ex vivo (P < 0.001). Our results indicate that SLex-OS exerts beneficial effects in traumatic shock states by blocking selectin-mediated leukocyte-endothelium interaction, thus improving survival, attenuating intestinal PMN accumulation, and diminishing shock-induced tissue injury.