Pathogenesis of Shigella Diarrhea XVI. Selective Targetting of Shiga Toxin to Villus Cells of Rabbit Jejunum Explains the Effect of the Toxin on Intestinal Electrolyte Transport

To examine the mechanism by which Shiga toxin alters intes-tinal water and electrolyte transport, ligated loops of rabbit jejunum were incubated in vivo with purified toxin and then studied in vivo by single pass perfusion and in vitro by the Ussing chamber voltage-clamp technique. Toxin exposure led to accumulation of water in the jejunal lumen, associated with decreased active basal NaCi absorption. Glucose- and alanine-stimulated Na absorption were also reduced, while toxin had no effect on either basal short-circuit current or the secretory response to theophylline. These observations suggest that Shiga toxin selectively inhibits NaCl absorption without sig-nificantly altering active anion secretion. To localize the cellu-lar site of toxin action, populations of villus and crypt cells from rabbit jejunum were isolated and studied. Villus cells had a greater content of the glycolipid Shiga toxin receptor, Gb3, had more toxin binding sites than did crypt cells, and were much more sensitive than crypt cells to toxin-induced inhibi-tion of protein synthesis. These experiments demonstrate that purified Shiga toxin inhibits jejunal fluid absorption.without affecting active fluid secretion by a preferential effect on villus cells. The results suggest that this is due to the differ-ential distribution of toxin receptors on villus compared to crypt cells