Protective effects of oligosaccharides in P-selectin-dependent lung injury.
Neutrophil recruitment into tissues is a multistep process involving sequential engagement of adhesion molecules, including selectins (E,P,L), which are reactive with oligosaccharides, and the family of beta 2 integrins which are reactive with endothelial intercellular adhesion molecules. These processes result in the initial rolling of leukocytes along the endothelial surfaces, followed by the firm attachment of leukocytes to the endothelium. The intravenous infusion of cobra venom factor into rats results in acute lung injury that is neutrophil-dependent, oxygen radical mediated and P-selectin-dependent. Here we report that infusion of sialyl-Lewis X, a ligand for P-selectin, dramatically reduced lung injury and diminished the tissue accumulation of neutrophils, whereas irrelevant oligosaccharides had no such effects. These results suggest that sialyl-Lewis X carbohydrates may be used as a new strategy for anti-inflammatory therapy.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Paulson
J C
JC
De Frees
S
S
Zheng
Z L
ZL
Lowe
J B
JB
Ward
P A
PA
D000818:Animals; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000037:antagonists & inhibitors; D016256:Lewis X Antigen / Q000494:pharmacology*; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats
D015815:Cell Adhesion Molecules; D004546:Elapid Venoms; D016256:Lewis X Antigen; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; C016310:cobra venom factor