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Pathogenesis of Shigella Diarrhea: Evidence for a Developmentally Regulated Glycolipid Receptor for Shigella Toxin Involved in the Fluid Secretory Response of Rabbit Small Intestine

Munir Mobassaleh, Arthur Donohue-Rolfe, Mary Jacewicz, Richard J. Grand and Gerald T. Keusch
The Journal of Infectious Diseases
Vol. 157, No. 5 (May, 1988), pp. 1023-1031
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30135707
Page Count: 9
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Pathogenesis of Shigella Diarrhea: Evidence for a Developmentally Regulated Glycolipid Receptor for Shigella Toxin Involved in the Fluid Secretory Response of Rabbit Small Intestine
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Abstract

Shigella toxin reproduces the major manifestations of shigellosis in ligated intestinal loops from adult rabbits and binds to a microvillus membrane (MVM) glycolipid receptor, globotriaosylceramide (Gba). Because neonatal human shigellosis is uncommon, we used the animal model for obtaining MVMs from rabbits of different ages to determine the presence of toxin receptors and Gba and to measure the fluid secretory response to toxin in ligated ileal loops. A single class of MVM receptors for 1251-labeled shigella toxin, first detected at 20 d of age, reached adult levels by 24 d (n = 1.7-23.8 x 10lVpg of protein; K = 1.1-3.8 x $10^9$ $M^{-9}$). Binding was specific for toxin subunit B. A toxin binding MVM glycolipid, identified as Gba, was detected in animals ≥ 16 d of age by high-performance thinlayer chromatography and autoradiography. Fluid secretion in response to shigella toxin in ligated small bowel loops occurred in temporal relation to the appearance of Gba, a result thus indicating the involvement of Gba in mediating the toxin effects.

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