In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds

There is accumulating evidence that sulfated lipids, sulfatedoligosaccharides and other sulfated compounds are reactive with selectinsin a manner that interferes with selectin interactions with their naturalligands. In the report we describe the ability of sulfated lipids(sulfatides and gangliosides) and multimeric forms of sulfated sialic acidto block binding of P- and E-selectin-Ig to neutrophils. The in vivoability of these compounds to block lung injury in rats following i.v.infusion of purified cobra venom factor (CVF), which induces injury that isL- and P-selectin dependent, was also determined as well as effects onrecruitment of neutrophils, as measured by lung myeloperoxidase. There wasa significant correlation between the ability of sulfated lipids and sialylcompounds to interfere in vitro with P-selectin-Ig binding to neutrophilsand to protect against P-selectin-dependent acute lung injury induced byCVF. The biological effects of these sulfated compounds were alsoassociated with diminished accumulation of neutrophils. The protectiveeffects of these compounds may be linked to their ability to interfere withP- selectin binding to counter-receptors on neutrophils.