In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds.
There is accumulating evidence that sulfated lipids, sulfated oligosaccharides and other sulfated compounds are reactive with selectins in a manner that interferes with selectin interactions with their natural ligands. In the report we describe the ability of sulfated lipids (sulfatides and gangliosides) and multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig to neutrophils. The in vivo ability of these compounds to block lung injury in rats following i.v. infusion of purified cobra venom factor (CVF), which induces injury that is L- and P-selectin dependent, was also determined as well as effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There was a significant correlation between the ability of sulfated lipids and sialyl compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to protect against P-selectin-dependent acute lung injury induced by CVF. The biological effects of these sulfated compounds were also associated with diminished accumulation of neutrophils. The protective effects of these compounds may be linked to their ability to interfere with P-selectin binding to counter-receptors on neutrophils.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Warner
R L
RL
Lowe
J B
JB
Smith
P L
PL
Suzuki
Y
Y
Miyasaka
M
M
Yamaguchi
S
S
Ohta
Y
Y
Tsukada
Y
Y
Kiso
M
M
Hasegawa
A
A
Ward
P A
PA
D000818:Animals; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism; D004546:Elapid Venoms / Q000633:toxicity; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019041:L-Selectin / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019087:Selectins / Q000187:drug effects* / Q000378:metabolism; D012794:Sialic Acids / Q000494:pharmacology*; D013431:Sulfates / Q000494:pharmacology; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D019040:E-Selectin; D004546:Elapid Venoms; D005732:Gangliosides; D019007:P-Selectin; D019087:Selectins; D012794:Sialic Acids; D013431:Sulfates; D013433:Sulfoglycosphingolipids; C016310:cobra venom factor; D019041:L-Selectin