PMID: 9655889Jul 10, 1998Paper

The carbohydrate sialyl Lewis(x) (sLe(x)) sulfated glycomimetic GM2941 attenuates glucan-induced pulmonary granulomatous vasculitis in the rat

The Journal of Pharmacology and Experimental Therapeutics
K S KilgoreJ S Warren

Abstract

We examined the protective effects of GM2941, a sulfated glycomimetic of the complex carbohydrate sialyl Lewis(x), in a model of pulmonary granuloma development. This study was based on the rationale that formation of glucan-induced lung granulomas is dependent on neutrophils and that sialyl Lewis(x) glycomimetic (GM2941) interferes, in vitro, with P-selectin-dependent neutrophil-endothelial adhesive interactions. Infusion of particulate yeast cell wall glucan into rats results in the rapid (48 hr) formation of monocyte/macrophage-rich angiocentric pulmonary granulomas. Development of granulomas exhibits a temporal pattern characterized by the early, transient influx of neutrophils into blood vessel walls at sites of glucan embolization, followed by accumulation of monocytes and macrophages that constitute the definitive angiocentric lesions. Within 1 hr after the infusion of glucan, immunohistochemical analysis revealed up-regulation of blood vessel wall-associated P-selectin. Previous studies utilizing neutrophil-depleted animals have revealed that neutrophils, although not present in definitive lesions, are required for full granuloma development. The potential of GM2941 to inhibit neutrophil-endothelial cell adhesive intera...Continue Reading

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