Study of staphylococcal toxic shock syndrome toxin in human epithelial cell culture

Staphylococcal toxic shock syndrome toxin (TST) inhibited growth of normal human epithelial (Chang) cells in culture, increasing the generation time 28% and 64% at concentrations of 4 X 10(-7)M and 8 X 10(-7)M, respectively. Fluorescence and electron microscopy of the cells treated with TST revealed the location of TST in the coated pits, specialized areas of the cell membrane known to contain high-affinity receptors for other polypeptide ligands. TST was labeled with 125I without detectable damage to the molecule and was shown to bind specifically to epithelial cells. A 100-fold excess of unlabeled TST inhibited binding of 125I-labeled toxin to the cells. Binding data indicated 10(4) receptor sites per cell for TST and a dissociation constant of 4 X 10(-9)M. Specific high-affinity binding of 125I-labeled TST to epithelial cells and the location of receptor sites in coated pits implies a possibility that the toxin is internalized by receptor-mediated endocytosis.