Sialyl Lewis X and anti-P-selectin antibody attenuate lipopolysaccharide-induced acute renal failure in rabbits.
OBJECTIVE
Acute renal failure (ARF) is one of the common problems associated with sepsis or multiple organ dysfunction syndrome (MODS). We have investigated the effects of inhibiting selectin-mediated cell adhesion on lipopolysaccharide-induced ARF in rabbits, using sialyl Lewis X oligosaccharide and PB1.3, an anti-human P-selectin monoclonal antibody, as inhibitors.


METHODS
ARF was induced by intravenous administration of lipopolysaccharide (0.3 mg/kg, i.v. bolus injection) to New Zealand White rabbits. Induction of ARF was characterized by increases in blood urea nitrogen (BUN), creatinine, and the number of polymorphonuclear leukocytes infiltrating glomeruli, and by fibrin deposition in glomeruli, and tubular dilatation in the kidney. Sialyl Lewis X oligosaccharide (14 mg/kg, i.v. bolus injection immediately before lipopolysaccharide administration and 9 mg/kg/h, i.v. infusion) or PB1.3 (5 mg/kg, i.v. bolus injection before lipopolysaccharide administration), anti-P-selectin antibody, were treated.


RESULTS
Treatment with sialyl Lewis X oligosaccharide inhibited the increases in BUN, creatinine, and the number of infiltrating polymorphonuclear leukocytes, and attenuated histopathological impairments. Similarly, treatment with PB1.3 prevented some of the characteristics associated with lipopolysaccharide-induced ARF, not but the increase in creatinine.


CONCLUSIONS
These results suggest that selectin inhibitors, including sialyl Lewis X oligosaccharide and PB1.3, may provide clinical benefits in the prevention of ARF associated with sepsis and MODS. To our knowledge, this is the first report that P-selectin is directly involved in lipopolysaccharide-induced ARF in rabbits.
Hayashi
H
H
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Imanishi
N
N
Ohnishi
M
M
Tojo
S J
SJ
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000473:pathology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009844:Oligosaccharides / Q000494:pharmacology*; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D011817:Rabbits; D000080506:Sialyl Lewis X Antigen
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D003404:Creatinine