FIGURE 8.

Two two‐hit models to explain cell type‐specific ricin sensitivity. Under normal conditions, dTHP‐1 cells exhibit ricin hypersensitivity (A), while A549 cells exhibit ricin hyposensitivity (B) based on the percent of cultured cells remaining alive after ricin challenge. We have identified ER stress and resulting activation of the unfolded protein response as a contributing factor to the unique sensitivity of dTHP‐1 cells, which are efficiently killed by cell‐autonomous ricin‐induced pro‐apoptotic signaling. Supplementation with TRAIL, a source of extrinsic pro‐apoptotic activation, is sufficient to induce cell non‐autonomous ricin hypersensitivity in A549 cells (C). Addition of TRAIL to dTHP‐1 cells had no effect on their response to ricin, further supporting their fully cell‐autonomous cell fate determination