Figure 4
Figure 4. Lumiliximab induces activation of Bax in CLL cells. (A) CLL cells treated with isotype control or lumiliximab for 4 hours were fixed, permeabilized, stained with anti-Bax NT polyclonal antibody followed by secondary anti–rabbit Ig-FITC, and analyzed by confocal microscopy. (B) Increasing levels of active Bax were detected by intracellular flow cytometry at 2 and 4 hours after treatment with lumiliximab but not in cells treated with isotype control. (C) Lumiliximab treatment induces the translocation of cytochrome c. Cytosol and mitochondria-enriched membrane fractions were prepared as described in “Subcellular fractionation” from isotype control or lumiliximab-treated cells. Samples were analyzed by immunoblot with antibodies against cytochrome c. (D) Summary of caspase inhibition data showing mean plus or minus SD (n = 3). (E) Caspase-9 activation induced by lumiliximab was blocked in the presence of caspase inhibitors z-VAD-fmk (ZVAD) and z-LEHD-fmk (LEHD), confirming the activity of the caspase inhibitors used in these experiments.

Lumiliximab induces activation of Bax in CLL cells. (A) CLL cells treated with isotype control or lumiliximab for 4 hours were fixed, permeabilized, stained with anti-Bax NT polyclonal antibody followed by secondary anti–rabbit Ig-FITC, and analyzed by confocal microscopy. (B) Increasing levels of active Bax were detected by intracellular flow cytometry at 2 and 4 hours after treatment with lumiliximab but not in cells treated with isotype control. (C) Lumiliximab treatment induces the translocation of cytochrome c. Cytosol and mitochondria-enriched membrane fractions were prepared as described in “Subcellular fractionation” from isotype control or lumiliximab-treated cells. Samples were analyzed by immunoblot with antibodies against cytochrome c. (D) Summary of caspase inhibition data showing mean plus or minus SD (n = 3). (E) Caspase-9 activation induced by lumiliximab was blocked in the presence of caspase inhibitors z-VAD-fmk (ZVAD) and z-LEHD-fmk (LEHD), confirming the activity of the caspase inhibitors used in these experiments.

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