Sialyl Lewisx-containing oligosaccharide exerts beneficial effects in murine traumatic shock.
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.
Skurk
C
C
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Buerke
M
M
Guo
J P
JP
Paulson
J
J
Lefer
A M
AM
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D007082:Ileum / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009584:Nitrogen / Q000378:metabolism; D009844:Oligosaccharides / Q000627:therapeutic use*; D019007:P-Selectin; D009195:Peroxidase / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000080506:Sialyl Lewis X Antigen
D009844:Oligosaccharides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D000080506:Sialyl Lewis X Antigen; D009195:Peroxidase; D009584:Nitrogen